Vascular endothelial growth factors (VEGFs) are regarded as the key vasculogenic mediators in the human body, of which VEGF-A is considered as one of the important types. It is the major growth factor possessing increasing vascular permeability as well as angiogenesis properties. This article provides intuition into the different effects of VEGF-A on vessels in ovarian hyper stimulation syndrome (OHSS) which is defined as a complication of in-vitro fertilization for infertility treatment, and obesity, a universally health problem. These are two dissimilar pathways outcomes for VEGF-A effects, thereby This article reviews updated information about the mentioned disorders and reveals that how this kind of growth factor yields different results on vasculature by activating distinct intracellular signaling in endothelial cells.

Background: Non-alcoholic fatty liver disease (NAFLD) is manifested by hepatic steatosis, insulin resistance, hepatocyte death, and systemic inflammation. Obesity induces steatosis and chronic inflammation in the liver. However, the precise mechanism underlying hepatic steatosis in the setting of obesity remains unclear. Here we report studies that address this question. Methods: 14 weeks on high-fat diet (HFD) with high sucrose, C57BL/6 mice revealed a phenotype of liver steatosis. Transcriptional profiling analysis of the liver tissues was performed using RNA sequencing (RNA-seq). Results: Our RNA-seq data revealed 692 differentially expressed genes involved in processes of lipid metabolism, oxidative stress, immune responses, and cell proliferation. Notably, the gene encoding neutral sphingomyelinase SMPD3, was predominantly upregulated in the liver tissues of the mice displaying a phenotype of steatosis. Moreover, nSMase2 activity was elevated in these tissues of the liver. Pharmacological and genetic inhibition of nSMase2 prevented intracellular lipid accumulation and TNFα-induced inflammation in in-vitro HepG2-steatosis cellular model. Furthermore, nSMase2 inhibition ameliorates oxidative damage by rescuing PPARα and prevent cell death associated with high glucose/oleic acid-induced fat accumulation in HepG2 cells. Conclusions: Collectively, our findings highlight the prominent role of nSMase2 in hepatic steatosis which could serve as a potential therapeutic target for NAFLD and other hepatic steatosis-linked disorders.

This article explores the relationship between metabolic syndrome and cardiovascular disease, providing a comprehensive overview of its risk factors and prevalence. Metabolic syndrome, characterized by a cluster of interconnected risk factors, significantly increases the likelihood of developing cardiovascular disease and type II diabetes. The study, conducted over a one-year period, involved 117 patients with ages between 30 to 79 years old. Various elements such as gender, age, education level, background, smoking, alcohol consumption, dietary aspects, physical activity, and their contribution in developing the metabolic syndrome, were analysed.Central adiposity and high blood pressure emerged as prominent elements of the condition. The findings underscore the importance of a healthy lifestyle in the prevention and management of metabolic syndrome. Encouraging regular physical activity, maintaining a balanced diet, rich in fresh vegetables and fruits, and avoiding harmful behaviours, such as smoking or alcohol consumption, are essential in reducing the risk of metabolic syndrome and its associated cardiovascular complications. The study highlights the need for public health initiatives, as well as individualized preventive strategies to combat the rising prevalence of metabolic syndrome. Through promoting awareness of its risk factors and implementing effective interventions, healthcare professionals can contribute to better cardiovascular health worldwide. Further research in this area will continue to enhance our understanding of the metabolic syndrome and refine preventive and therapeutic approaches for its management.

Obesity and metabolic syndrome involve chronic low-grade inflammation called metabolic inflammation as well as metabolic derangements from increased endotoxin and free fatty acids. It is debated whether the endoplasmic reticulum (ER) stress in monocytic cells can contribute to amplify metabolic inflammation; if so, by which mechanism(s). To test this, metabolic stress was induced in THP-1 monocytic cells by treatments with lipopolysaccharide (LPS), palmitic acid (PA), or oleic acid (OA), in the presence or absence of ER stressor thapsigargin (TG). Gene expression of tumor necrosis factor (TNF)-α and markers of ER/oxidative stress was determined by qRT-PCR, TNF-α protein by ELISA, ROS by DCFH-DA assay, HIF-1α/p38/ERK-1,2/NF-κB phosphorylation by immunoblotting, and insulin sensitivity by glucose-uptake assay. Regarding clinical analyses, adipose TNF-α was assessed by qRT-PCR/IHC and plasma TNF-α/hs-CRP/MDA/OX-LDL by ELISA. We found that the cooperative interaction between metabolic and ER stresses promoted TNF-α, ROS, CHOP, ATF6, SOD2, and NRF2 expression (P≤0.0183),. However, glucose uptake was not impaired. TNF-α amplification was dependent on HIF-1α/p38/NF-κB phosphorylation, while MAPK/NF-κB inhibitors and antioxidants/ROS scavengers attenuated TNF-α production (P≤0.05). Individuals with obesity displayed increased adipose TNF-α gene/protein expression as well as elevated plasma levels of TNF-α, CRP, MDA, and OX-LDL (P≤0.05). Our findings support a cooperative interaction between metabolic and ER stresses, favoring inflammation by triggering TNF-α production via the ROS/CHOP/HIF-1α and MAPK/NF-κB dependent mechanisms. This study also shows the therapeutic potential of ROS scavengers/anti-oxidants in inflammatory conditions involving metabolic/ER stresses.

It is now well accepted that most chronic diseases have a common feature which is “low-grade” inflammation. Whether inflammation is causal or rather consequent to these diseases is still a matter of debate. A key factor of inflammation is considered to be “oxidative stress”, which is the result of an alteration of redox homeostasis which is critical for the regulation of physiological cell and organ metabolism and proliferation. The term “oxidative stress” is how-ever often used in an inappropriate manner as the primary target of the initial oxidative radical, superoxide ion, is nitric oxide which, being in large excess, acts as a “buffer”, yielding reactive nitrogen species. It is only once the superoxide fluxes exceed the nitric oxide fluxes that true “oxidative stress” occurs. Nitro-oxidative stress is a more appropriate term which takes into account the evolving generation of reactive nitrogen and oxygen species and their effects on cell and organ pathophysiology. The molecular bases of redox homeostasis and nitro-oxidative stress will be presented and discussed using obesity-linked inflammation as a path-ophysiological example.

Leucine-rich α-2 glycoprotein1 (LRG1) is a member of the leucine-rich repeat (LRR) family that was implicated in multiple diseases including cancer, aging and heart failure as well as diabetes and obesity. LRG1 plays a key role in diet-induced hepatosteatosis and insulin resistance by mediating the crosstalk between adipocytes and hepatocytes. LRG1 also promotes hepatosteatosis by upregulating de novo lipogenesis in the liver and suppressing fatty acid β oxidation. In this study, we investigated the association of LRG1 with obesity markers including leptin and other adipokines in adolescents (11-14 years; n=425). BMI-for-age classification based on WHO growth charts was used to define obesity. Plasma LRG1 was measured by ELISA while other markers were measured by multiplexing assay. Median (IQR) of LRG1 levels was higher in obese [30 (25, 38) µg/mL] and overweight [30 (24, 39) µg/mL] adolescents, compared to normal-weight participants [27 (22, 35) µg/mL]. The highest tertile of LRG1 had an OR [95%CI] of 2.55 [1.44, 4.53] for obesity. LRG1 was positively correlated to plasma levels of HsCRP (R=0.2), Leptin (R=0.2) and Chemerin (R=0.24) with p<0.001. Additionally, it was positively associated with plasma level of IL6 (R=0.17) and IL10 (R=0.14) but not TNF-α. In conclusion, LRG1 levels are increased in obese kids and associate with increased levels of adipogenic markers. These results suggest the usefulness of LRG1 as an early biomarker for obesity and its related pathologies in adolescents.

Infectious as well as most non-infectious diseases share certain common molecular mechanisms. Among them, oxidative stress and the subsequent inflammatory reaction are of particular note. Metabolic disorders induced by external agents, be they bacterial or viral pathogens, excessive calorie intake, poor-quality nutrients, or environmental factors, produce an imbalance between the production of free radicals and endogenous antioxidant systems; the consequence being the oxidation of lipids, proteins and nucleic acids. Oxidation and inflammation are closely related, and whether oxidative stress and inflammation represent the causes or consequences of cellular pathology, they produce metabolic alterations that influence the pathogenesis of the disease. In this review we highlight two key molecules in the regulation of these processes: Paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2). PON1 is an enzyme bound to high-density lipoproteins. It breaks down lipid peroxides in lipoproteins and cells, participates in the protection conferred by HDL against different infectious agents, and is considered part of the innate immune system. With PON1 deficiency, CCL2 production increases, which induces migration and infiltration of immune cells in target tissues, and is involved in disturbing normal metabolic function. This disruption involves pathways controlling cellular homeostasis as well as metabolically-driven chronic inflammatory states. Hence, an understanding of these relationships would help improve treatments and, as well, identify new therapeutic targets.

Administration of crude polysaccharides extract from natural product is a promising gut microbiota-targeted approach to preventing obesity and associated metabolic disorders. Dietary restrictions can change the type and number of gut bacteria, which is an important factor in delaying the onset and burden of diseases. This study aimed to investigate the effects of high-yield crude polysaccharides from Cordyceps militaris (CMP) on high-fat diet (HFD) mice model and the gut microbiota community assembly, and to identify whether selenium (Se) addition would improve CMP action mode during cultivation. We found that the CMP treatment ameliorated adipose and liver pathologic morphology and fat accumulation in obese mice, while, SeCMP intervention was not superior than CMP in body mass gain, but notably decreasing serum triglyceride level increased by HFD. The upregulated expression of gene Cyp7a1 in liver and protein UCP1 in brown adipose tissue (BAT) preliminary indicated that the effect might relate to bile acids (BAs) metabolism pathway and thermogenesis. In addition, CMP showed a drastic decrease in the gut microbes which positively correlated with dyslipidemia parameters. Our result reveals the potential of CMP to be used as functional food in the prevention of diet-induced adipose and liver steatosis, so does SeCMP has outstanding capacity of improving dyslipidemia.

Obesity is a global public health problem and the environment as its major determinant. To identify interventions an evidence base is warranted. To this aim we investigate the relationship between the consumption of foods and eating locations (like home, school/work and others) in British adolescents, using data from the UK National Diet and Nutrition Survey Rolling Program (2008–2012 and 2013-2016). Cross-sectional analysis of 62,523 food diary entries from this nationally representative sample then focused on foods contributing up to 80% total energy to the daily adolescent´s diet. Correspondence Analysis (CA) was first used to generate food-location relationship hypotheses and Logistic Regression (LR) to quantify the evidence in terms of odds ratios and formally test those hypotheses. The less-healthy foods that emerged from CA were chips, soft drinks, chocolate and meat pies. Adjusted Odds Ratios (99% CI) for consuming specific foods at a location “Other” than home (H) or school/work (S) in the 2008-12 survey sample were: for soft drinks 2.8 (2.1 to 3.8) vs. H and 2.0 (1.4 to 2.8) vs. S; for chips 2.8 (2.2 to 3.7) vs. H and 3.4 (2.1 to 5.5) vs. S; for chocolates 2.6 (1.9 to 3.5) vs. H and 1.9 (1.2 to 2.9) vs. S; and for meat pies 2.7 (1.5 to 5.1) vs. H and 1.3 (0.5 to 3.1) vs. S. These trends were confirmed in the 2013-16 survey sample. Interactions between location and BMI were not significant in either sample. In conclusion, our study showed that adolescents are more likely to consume specific less-healthy foods at locations away from home and school/work, irrespective of BMI. Such locations include leisure places, food outlets and “on the go”, hence public health policies to discourage less-healthy food choices in these locations is warranted for all adolescents.

Preventing childhood obesity and associated comorbidities is often hampered by disproportionate disparity in healthcare provision in minority ethnic populations. This study contextualised lifestyle factors influencing childhood obesity and related comorbidity from the perspectives and experiences of parents of ethnic minority children with obesity comorbidity. Families of Black, Asian and Minority Ethnicities (BAME) in the Northeast of England (n=180) were contacted, and families with a child diagnosed with obesity and comorbidity (non-alcoholic fatty liver disease, musculoskeletal problems, respiratory disorder, or polycystic ovarian disease) were interviewed (n=11). Semi-structured interviews and qualitative thematic analysis included parents’ perspective and experience on how their children were impacted by obesity and comorbidities, healthcare preventative interventions including lifestyle physical activity and nutrition, and views on tackling obesity. Parents’ perspectives and experience revealed eleven themes centred around living with a child with obesity, risks and impact of obesity diseases; access to lifestyle nutritional and physical activity, and ethnicity specific barriers. Parents revealed social disadvantage, fear of victimisation by social services, perceptions on their cultural and religious traditions when dealing with nutrition and exercise, and child’s weight racial stigmatisation. Parents reported closer bonding with their children than health authorities to protect from obesity consequences. Work pressure, time, and lack of professionals’ guidance were seen as barriers to healthy lifestyle, while support from friends and family bond in adopting healthy lifestyle behaviours were facilitators. Parents reported no awareness of health service provision of nutritional and physical activity obesity prevention programmes. Minority ethnic communities’ perspective on childhood obesity prevention does not match the healthcare system preventative offerings. Community and family-oriented obesity preventative approaches, especially lifestyle nutrition and physical activity interventions are needed beyond those administered by the primary healthcare system.

This review focuses on the emerging evidence for the association between estimated cardiorespiratory fitness (eCRF) and metabolic risk factors. Given the challenges associated with directly measuring cardiorespiratory fitness (CRF) in large populations, eCRF presents a practical alternative for predicting metabolic health risks. A literature search identified six relevant cohort studies from 2021 to 2024 that investigated the association of eCRF with hypertension, hyperglycemia, dyslipidemia, and obesity. The review findings highlight a consistent inverse relationship between higher eCRF and lower incidence of metabolic risks in line with CRF cohort studies. This review highlights the importance of low eCRF as a primordial indicator for metabolic risks and underscores the need for broader application. Future research directions should include exploring eCRF's predictive accuracy across diverse populations and health outcomes and testing its real-world applicability in healthcare and public health settings.

Excess consumption of a high-fat diet has been identified as one of the contributing factors for obesity. Women are at higher risk for adult obesity than men, predisposing them to a different set of detrimental disease conditions. Furthermore, aging studies show that physiological decline also has a serious impact on changes in the endocrine properties of white adipose tissue. Howev-er, there is still relatively little known about the factors associated with obesity and aging and their compounding impact on women’s health. To investigate adipocytokine secretion profile changes, female C3H/HeJ mice were induced to obesity through long-term consumption of a high-fat diet. Weight gain measurements and Echo MRI analysis of fat composition showed in-creases were a due solely to the high fat content in the diet. Adipocytokine secretions were ana-lyzed in media conditioned from harvested visceral fat tissue that was organ cultured ex-vivo. Adipocytokine analysis across diets and age showed significant increases in Adiponectin and Leptin secretion in high-fat diets, accelerated increases in Resistin secretion with high-fat diets. Aging induced increased secretion of Lipcalin-2, Pentraxin-3 and Serpin E1, MCP-1 and ICAM-1, regardless of diet. Furthermore, comparisons of organoid cultured protein secretions and flash-frozen tissue samples differed greatly, suggesting the WAT organoid cultures may yield information more reflective of in situ conditions. Taken together, our results show that diet and aging significantly impact secretions from adipose tissue, that may contribute to women’s health issues.

Obesity is a worldwide epidemic; hence it is crucial to understand how it can be effectively prevented/treated. Thus, obesity should be tackled considering that it is a multifactorial condition. This work examines a wide range of factors and attempts to understand which contribute most to variability in overweight/obesity. Eighty-four subjects with overweight/obesity were recruited. Dietary baseline information was obtained by analyzing three 24-hour recalls. Resting metabolic rate was measured using indirect calorimetry, physical activity through accelerometry, cardiometabolic parameters were determined in blood samples and body composition by anthropometry and bioimpedance. Factor analysis of principal components (PCA) was carried out (SPSS v22.0). Large interindividual variability was observed in dietetic, biochemical, and physical activity measurements (coefficient of variation ≥30%), but body composition was homogeneous. Volunteers had an unbalanced diet and low physical activity. PCA reduced the 26 analyzed variables into 7 factors, accounting for 81,5% of total data variability. The main factor was the ‘‘caloric and lipid factor’’ related to diet, responsible for 25.9% of total variability, followed by ‘‘adiposity factor’’ (16,9%) and ‘‘cardiometabolic risk factor’’ (13,2%). Diet seems to be the factor that contributes the most to data variability in people with overweight/obesity, especially the intake of lipids, energy and proteins.

A Pediatric Sleep Questionnaire (PSQ) and a recording of the respiratory parameters with a noc-turnal home cardiorespiratory polygraphy (PG) are necessary to diagnose OSAS. Few researchers have studied how obesity could influence the respiratory parameters in OSAS children. The aim of the study was to investigate how obesity can influence sleep respiratory parameters in OSAS children. Methods: The study analyzes 56 Caucasian children and adolescents aged 11 ± 2.79 years with a BMI> 5th percentiles and PSQ value of 0.33. Children were divided into the Obesity Group (OG) with a BMI of  95th and the Control Group (CG) with a 5th<BMI> 95th percentile. All selected children underwent PG. Respiratory parameters were extracted to divide into levels of severity OSAS: snoring, mild, moderate, and severe. Results: The comparison analysis of AHI, SaO2, and Nadir between the OG and CG showed a statistical significance only for ODI (p = 0.02). The comparison analysis of PSQ between the OG and CG and of PSQ and respiratory parameters showed no significant result. A statistically significant correlation between BMI and AHI (r2=0.01), SaO2 (r2=0.09), and Nadir O2 (r2=0.00) was found. Conclusion: There was no strong correlation between Obesity and OSAS, but it was found between BMI increasing and AHI severity

Recently, “mature” silkworms (MS) of Bombix mori have been considered as a potential nutraceutical, with a number of health benefits reported for steamed and lyophilized MS powder (SMSP). However, no obesity-related effects have been reported for SMSP. In the present study, anti-obesity effects of SMSP were investigated in adult mice in vivo, aged 12 weeks at the onset of drug administration, fed normal diet (ND) and high-fat diet (HFD), respectively, for 12 weeks. SMSP significantly suppressed body weight gain, intra-abdominal adipose tissue, and food efficiency in both ND-fed and HFD-fed adult mice. In addition, SMSP significantly decreased food intake and liver weight in HFD-fed mice, indicating that SMSP suppressed appetite and simultaneously reduced the conversion of feed into body weight in HFD-fed mice. SMSP also significantly lowered serum levels of glucose, triglyceride, total cholesterol, low-density lipoprotein cholesterol, asparagine transaminase, alanine transaminase, and alkaline phosphatase. However, SMSP had no significant effect on the weights of kidney, spleen, and thymus and serum levels of blood urea nitrogen and creatinine. Taken together, the above results suggest that SMSP has potent anti-obesity effects and is safe for long-term use as a potential therapeutic and/or nutraceutical in both obese patients and non-obese individuals.

Non-pharmacologic options like the ketogenic diet (KD) and intermittent fasting (IF) are practical nutritional interventions with minor reported side effects like gastrointestinal symptoms, dyslipidemia, and hypomagnesemia for various medical ailments. In conjunction with IF, KD shows promise in weight loss, diabetes management, cardiovascular disorders, polycystic ovarian syndrome, cancer, and chronic neurological disorders. Based on prior research, we have examined the mechanism of action of KD and IF and their effect on neurological diseases, cancer, and obesity. We have also suggested evidence-based recommendations for the safer practice of KD and IF. Despite potential benefits, long-term adherence to KD poses challenges. Periodic KD implementation may thus benefit newly diagnosed overweight or obese patients with type 2 diabetes mellitus, aiding blood glucose and lipid management while promoting weight loss. KD is a high-fat and low-carbohydrate diet with a ratio of fat to carbohydrates and protein being 4:1 or 3:1, and thus, for peripheral tissues and the brain, fatty acids become the mandatory source of cellular energy. Ketone bodies have been used as the primary energy source during fasting. KD has been utilized as an effective treatment for refractory epilepsy since the 1920s. Evidence of the neuroprotective role of KD in diseases like epilepsy, stroke, traumatic brain injury, Alzheimer’s disease, and other neurological diseases has been noted. Since the 1960s, KD has become a popular method for obesity treatment. In addition, KD has been suggested as a potent anticancer therapy when used alone or as an adjuvant. KD may increase tumor cell sensitivity when combined with classic chemotherapy and radiotherapy. Thus, the probability that modifying the diet can help manage obesity, cancer, and chronic neurological disease without depending on pharmacological treatment and their serious side effects for a lifetime is promising and requires further investigation. KD holds promise as a potential adjunctive therapy in various neurological disorders, offering new avenues for treatment and neuroprotection. IF has shown potential in slowing the progression of neurodegenerative diseases such as Alzheimer's and Parkinson's by promoting antioxidant defense and suppressing inflammation. KD and IF show promise in cancer therapy by targeting altered cancer cell metabolism. Additionally, KD may enhance the effects of standard treatments like chemotherapy and radiotherapy. Some of the most robust reports of keto's possible benefits have come from glioblastoma, a very aggressive brain cancer. KD has also shown strong evidence for its effectiveness in weight loss, mainly attributed to its appetite-suppressing action in ketosis. However, long-term adherence to KD can be challenging, and periodic KDs may help manage blood glucose and lipid levels in overweight or obese patients with type 2 diabetes mellitus. Likewise, IF may be more effective than regular calorie restriction for achieving weight loss goals when combined with exercise programs. More prospective human studies are warranted to evaluate both KD and IF's potential therapeutic effectiveness and safety.

Bioactive fractions were isolated from the leaves extract of Kalanchoe pinnata and subjected to scrutiny for their prospective anti-obesity properties. An array of in vitro phytochemical, antioxidant, and enzyme inhibition assays were executed, which dis-cerned fractions F1 and F2 as the most effective fractions. These fractions were sub-sequently studied through in vivo experiments, affirming that F2 as the most potent fraction. Further characterization of F2 was conducted via HPTLC MS-MSn tech-niques. The outcomes demonstrated that F2 produced a notable anti-obesity effect in obese mice, reducing their body weight and lipid metrics, and leading to advanta-geous changes in their organs. An analytical examination of F2 revealed the existence of four principal compounds, which were subsequently subjected to in silco molecular docking and dynamic analysis, confirming their aptitude for binding to selected pro-teins. These findings imply that the utilization of Kalanchoe pinnata leaves could pro-vide a promising therapeutic strategy for the treatment of obesity.

Background: There is an exponential increase in caesarean sections with epidemic proportions worldwide, which is considered as a serious public health issue that influences negatively both maternal and childhood health. Aims: This study aimed to evaluate the associations between pre-dominant maternal risk factors and the prevalence of caesarean section in a representative sample of women from Greece. Methods: This is a cross-sectional study conducted on 5182 healthy, re-productive-aged women from 11 geographically diverse Greek areas after applying specific inclu-sion and exclusion criteria. Statistical analysis was applied to evaluate the impact of maternal so-ciodemographic, anthropometric, lifestyle and perinatal factors in the risk of caesarean section de-liveries. Results: A high prevalence of 56.4% of caesarean section deliveries was recorded in the study population. The incidence of caesarean sections reached to 51.5% in private hospitals in which an increasing rate of 47.5% for planned caesarean sections were noticed. Older maternal age, pre-pregnancy overweight and obesity, excess gestational weight gain, high rates of preterm birth, better economic status, smoking habits, and private type of birth hospital were significantly related with enhanced risk of caesarean section, independently of multiple confounding factors. Conclu-sions: Our study revealed that caesarean section rates are continuously increase, while several maternal risk factors, including especially pre-pregnancy overweight/obesity and excess gestational weight gain, cumulatively raise its prevalence which further increase the risk for postnatal adverse outcomes for both the mothers and their children. Emergent public health policies and strategies should be promoted to confront the predominant maternal risk factors-related with caesarean sec-tion and inform future mothers how to be prevented from them by applying healthier nutritional and lifestyle habits and to select caesarean section only due to emergency medical reasons. Alarmingly enough, targeted nutritional intervention strategies are strongly recommended to ef-fectively reduce the prevalence of maternal pre-pregnancy overweight/obesity and the excess gestational weight gain, which in turn may minimize the risk of childhood overweight/obesity.

Background: Pre-pregnancy overweight and obesity of women of childbearing ages, has alarmingly a growing trend in developed countries. This study aimed to evaluate potential associations between maternal pre-pregnancy excess body weight and childhood demographic and anthropometric characteristics, as well as perinatal and postnatal outcomes. Methods: This is a cross-sectional study conducted on 5198 pre-school children aged 2-5 years old and their matched mothers that were enrolled from nine different Greek regions. Maternal and childhood anthropometric and demographic data, perinatal and postnatal outcomes were collected from medical history records or validated questionnaires. Results: A prevalence of 24.4% and 30.6% of overweight/obesity was recorded for the enrolled children and their mothers 2-5 years postpartum. In multivariate analysis, childhood overweight and obesity was significantly more frequently observed when maternal pre-pregnancy BMI status was overweight or obese [OR: 2.11 (1.80-2.42) p=0.0001]. A high prevalence of caesarean section delivery and childhood diabetes type I was also significantly associated with maternal pre-pregnancy overweight/obesity [OR:1.71 (1.33-2.19) p=0.0175) and OR: 1.27 (1.04-1.53) p=0.0014, respectively]. Conclusions: Maternal pre-pregnancy overweight and obesity rates were related with increased childhood weight status at birth and 2-5 years postpartum, highlighting the necessity of encouraging healthy lifestyle promotion, including healthier nutritional habits, and focusing on obesity population policies and nutritional interventions among women of reproducible age.

Vitamin C status is known to be associated with several demographic and lifestyle factors. These include gender, age, ethnicity, pregnancy/lactation, body weight, smoking status and dietary habits. In the present study, our aim was to interrogate the National Health and Nutrition Examination Survey (NHANES) 2017-2018 datasets to assess the impact of these factors on vitamin C dose-concentration relationships to establish if there are higher requirements for vitamin C in certain subpopulations and the possible extent of these additional requirements. The relevant data were extracted from the NHANES 2017-2018 datasets, the final cohort of which comprised 2828 non-supplementing adult males and females (aged 18 – 80+ years) with both vitamin C serum concentrations and dietary intake data available. The data was subsequently stratified by gender, age tertiles (≤36, 37-58, ≥59 years), ethnicity (non-Hispanic white, non-Hispanic black, and total Hispanic), socioeconomic tertiles (poverty income ratios: &gt;3.0, 1.36 – 3.0, ≤1.35), weight tertiles (≤72, 72-91, ≥91 kg), BMI tertiles (≤26, 26-32, ≥32 kg/m2) and smoking status. Sigmoidal (four parameter logistic) curves with asymmetrical 95% confidence intervals were fitted to the dose-concentration data. We found that males required vitamin C intakes ~1.2-fold higher than females to reach ‘adequate’ serum concentrations of 50 µmol/L. Males had both higher body weight and a higher prevalence of smoking than females. Smokers required vitamin C intakes ~2.0-fold higher than non-smokers to reach adequate vitamin C concentrations. Relative to adults in the lighter weight tertile, adults in the heaver weight tertile required ~2.0-fold higher dietary intakes of vitamin C to reach adequate serum concentrations. We did not observe any impact of ethnicity or socioeconomic status on the vitamin C dose-concentration relationship, and although no significant difference between younger and older adults was observed at vitamin C intakes &gt; 75 mg/day, at intakes &lt; 75 mg/day, older adults had an attenuated serum response to vitamin C intake. In conclusion, certain demographic and lifestyle factors, specifically gender, smoking and body weight, have a significant impact on vitamin C requirements. Overall, the data indicate that the general population must consume ~110 mg/day of vitamin C to attain adequate serum concentrations, smokers require ~165 mg/day relative to non-smokers, and heavier people (100+ kg) require ~155 mg/day to reach the same vitamin C concentrations. These findings have important implications for global vitamin C dietary recommendations.

Higher body weight is known to negatively impact plasma vitamin C status. However, despite this well-documented inverse association, recommendations on daily vitamin C intakes by health authorities worldwide do not include particular reference values for people of higher body weight. This suggests that people of higher body weight and people with obesity may be insufficient in vitamin C in spite of ingesting the amounts recommended by their health authorities. The current preliminary investigation sought to estimate how much additional vitamin C people with higher body weights need to consume in order to attain a comparable vitamin C status to that of a lower weight person consuming an average Western vitamin C intake. Data from two published vitamin C dose-concentration studies were used to generate the relationship: a detailed pharmacokinetic study with seven healthy non-smoking men and a multiple depletion-repletion study with 68 healthy non-smoking men of varying body weights. Our estimates suggest that an additional intake of 10 mg vitamin C/day is required for every 10 kg increase in body weight to attain a comparable plasma concentration to a 60 kg individual with a vitamin C intake of ~110 mg/day, which is the daily intake recommended by the European Food Safety Authority (EFSA). Thus, individuals weighing e.g. 80 and 90 kg will need to consume ~130 and 140 mg vitamin C/day, respectively. People with obesity will likely need even higher vitamin C intakes. As poor vitamin C status is associated with increased risk of several chronic diseases including cardiovascular disease, these findings may have important public health implications. As such, dose-finding studies are required to determine optimal vitamin C intakes for overweight and obese people.

The rise in prevalence of obesity in women of reproductive age in both developed and developing countries might propagate intergenerational cycles of detrimental effects on metabolic health, contributing to substantial economic burden on society. Placental lipid metabolism might be disrupted by maternal obesity, which possibly affects the life-long health of the offspring. Here, we investigated placental lipid metabolism and handling from women with pre-gestational obesity as a sole pregnancy complication and compared to placental responses of lean women. Open profile and targeted lipidomics were used to assess placental lipids and oxidized products of docosahexahenoic acid (DHA), neuroprostanes, and arachidonic acid (AA), isoprostanes. Placental fatty acid transporters FABP1, FABP3 and endothelial lipase protein were measured. Despite no signs of overall alterations in lipid content, increased contents of DHA, AA, DHA-derived neuroprostanes and AA-derived isoprostanes and decreased content of FABP1 protein were found in placentas from obese women. Multivariate analyses suggested that these oxidised fatty acids are associated with maternal and placental inflammation and also with birth weight. These results might shed light on the molecular mechanisms associated with altered fatty acid metabolism and lipid handling in maternal pre-gestational obesity, placing these oxidized fatty acids as novel mediators of placental function.

This scoping review investigated how consumers perceive and interpret serving size information on food packages. A search of seven databases (2010 to September 2017) was followed by title and abstract screening, with relevant articles assessed for eligibility in full-text. Fourteen studies met inclusion criteria, with relevant data extracted by one reviewer and checked for consistency by a second reviewer. Five studies reported poor understanding of nutrition facts labelling and portion size, with information to ‘benchmark’ serving size against reported as helpful in two studies. Consumer attitudes towards serving size labelling were measured in six studies and identified that serving size information was interpreted as indicative of nutrient intake regardless of portion size recommendations. Increased labelled serving sizes resulted in increased portion sizes in three studies, with three studies reporting the opposite or neutral effect for discretionary food portion sizes. The influence of labelled serving size on consumer attitudes and consumption is complex and sometimes counterintuitive. As labelled serving size can impact on consumption, any changes may result in unintended public health consequences. The effects of labelled serving size format changes should be tested carefully within experimental and ecological contexts and accompanied by tailored, comprehensive and serving size-specific food literacy initiatives.

IL1RA intron 2 86-bp repeat and IL4 intron 3 70-bp repeat are VNTRs that have been associated with various diseases, but their role in obesity is elusive. The objective of this study was to investigate the association of IL1RA and IL4 VNTRs with obesity and adiposity in 315 Malaysian subjects (128 M/187 F; 23 Malays/251 ethnic Chinese/41 ethnic Indians). The allelic distributions of IL1RA and IL4 were significantly different among ethnicities, and the alleles were associated with total body fat (TBF) classes. Individuals with IL1RA I/II genotype or allele II had greater risk of having higher adiposity - even after controlling for ethnicity [Odds Ratio (OR) of I/II genotype = 12.21 (CI = 2.54, 58.79; p = 0.002); II allele = 5.78 (CI = 1.73, 19.29; p = 0.004)]. However, IL4 VNTR B2 allele was only significantly associated with overall adiposity status before adjusting for ethnicity [OR = 1.53 (CI = 1.04, 2.23; p = 0.03)]. TBF was also significantly higher in those with IL1RA II allele compared with I allele (31.79 ± 2.52 vs. 23.51 ± 0.40; p = 0.005). Taken together, IL1RA intron 3 VNTR seems to be a genetic marker for overall adiposity status in Malaysian subjects.

Background. Type 2 diabetes mellitus (T2DM) is becoming a major global health concern, especially in poorer nations. The high prevalence of obesity and the ensuing diabetes I attributed to rapid economic progress, physical inactivity, consumption of high-calorie foods, and changing lifestyles. Objectives. We investigated the role of interleukins-10 , 19 and 22 with varying levels of obesity in T2DM in the Asir region of Saudi Arabia. Materials and methods. 170 confirmed T2DM patients and a control group were enrolled. The demographic data, serum levels of IL-10, IL-19, and IL-22, and biochemical indices were assessed in patients and control groups by standard procedures. Results. T2DM patients were divided into four groups: A (normal body weight), B (Overweight), C (obese), and D (highly obese). Both male and female T2DM subjects in Group A showed significant decreases in IL-10 levels as compared to controls; however, there were insignificant changes in IL-10 levels in Groups C and D. T2DM patients in groups C and D, in both males and females, depicted very significant (p 0.001) increases in IL-19 levels as compared to controls and group A. Patient groups A to D displayed a progressive elevation of Il-22 levels irrespective of gender, although significant alterations were seen only in groups B to D, with p 0.05 for group B and p 0.01 for groups C and D respectively, as compared to healthy controls. Conclusions. IL-10 showed a strong relationship with T2DM in males with varying degrees of obesity, but females depicted relatively higher IL-10 levels in obese and highly obese groups, pointing to a protective phenomenon. IL-19 levels showed significant increases in all four groups, irrespective of gender. IL-22 appears to be unrelated to T2DM per se but shows an association with varying degrees of obesity.

Keywords: bariatric surgery, sleeve gastrectomy, Roux-en-y gastric bypass, obesity, microbiota, gut-brain axis, beck scale, depression, diet, probiotics

Abstract: The brain endothelial cell (BEC) glycocalyx (ecGCx) is a BEC surface coating consisting of a complex interwoven polysaccharide (sweet husk) mesh-like network of membrane-bound proteoglycans, glycoproteins, and glycosaminoglycans (GAGs) covering the apical luminal layer of the brain endothelial cells. The ecGCx may considered as the 1st barrier of a tripartite blood-brain barrier (BBB) consisting of 1) ecGCx; 2) BECs; (3) extravascular compartment of pericytes, extracellular matrix, and perivascular astrocytes, Perturbations of this barrier allow for increased permeability in the postcapillary venule that will be permissive to both fluids, solutes, and proinflammatory peripherally-derived leukocytes into the perivascular spaces (PVS) to result in enlargement as well as increased neuroinflammation. The ecGCx is known to have multiple functions, which include its physical and charge barrier, mechanical transduction, regulation of vascular permeability, modulation of inflammatory response, and anticoagulation functions. This review discusses each of the listed functions in detail and utilizes multiple transmission electron micrographs and illustrations to allow for a better understanding of the ecGCx structural and functional roles as it relates to enlarged perivascular spaces (EPVS). This is the 5th review of a series quintet that discuss the importance of EPVS from the perspective of the cells of brain barriers. Attenuation and/or loss of the ecGCx results in brain barrier disruption with increased permeability to proinflammatory leukocytes, fluids and solutes, which accumulate in the postcapillary venule perivascular spaces. This accumulation results in obstruction and results in EPVS with impaired waste removal of the recently recognized glymphatic system. Importantly, EPVS are progressively being regarded as a marker of cerebrovascular and neurodegenerative pathology.

In New Orleans, Louisiana the population’s poor baseline health led to its establishment as an early epicenter for severe acute COVID-19. Antici-pating future outbreaks of COVID-19 and other respiratory viruses, we need to identify correlates of outcome, from real clinical experience. 89 patients were recruited into the ClinSeqSer acute COVID-19 longitudinal observational study, from the beginning of the outbreak in March to July 2020. Patients admitted for acute COVID-19 were enrolled in person. The cohort is unique as it is 68% Black, 53% female, of average age of early 60s, and prevalence of obesity and hypertension respectively of 55% and 83%. The outcomes are: 53% severe (20% fatal, 33% non-fatal) and 47% non-severe, with severe defined as death or requiring mechanical ventila-tion or high flow oxygen. Obesity and admit systolic blood pressure (SBP) >140mmHg are each associated with severe outcome and, despite respective sensitivity of 71% and 76%, specificity ~66% for both, and ac-curacy of 60% and 70% by ROC analysis, would likely provide useful predictors of outcome in critically stressed health care systems. We discuss pathophysiologic hypotheses to explain why high admit SBP is observed only in half of patients with pre-COVID hypertension and is associated with severe outcome.

Insulin-like growth factor binding proteins (IGFBPs) are critical modulators of the metabolism. In adults, IGFBPs are associated with obesity and insulin resistance but the association of IGFBPs with metabolic homeostasis in children and adolescents is not fully characterized. In this study we investigated the association of plasma IGFBPs (IGFBP-1, 3 and 7) with weight status, central adiposity and cardiovascular disease markers Hs-CRP and Ox-LDL. A total of 420 adolescents (age 11-14 years) were randomly recruited from public middle schools in Kuwait. IGFBPs were measured using bead-based multiplexing while Hs-CRP and Ox-LDL were measured using ELISA. IGFBP-1 levels were significantly lower in obese and overweight participants compared to normal weight children. Only IGFBP-1 was negatively associated with waist circumference to height (WC/Ht) ratio. IGFBP-1 was negatively correlated with Hs-CRP while IGFBP-3 and IGFBP-7 were negatively correlated with Ox-LDL. These data demonstrate a robust negative association of IGFBP-1, but not IGFBP-3 or -7, with overweight and obesity, and the inflammation marker Hs-CRP. Central adiposity (WC/Ht ratio) was a stronger predictor of IGFBP-1 than BMI-for-age z-score. IGFBP-1 could thus be used as a sensitive predictive diagnostic tool for obesity and its subsequent effects in screening and monitoring of obesity-related metabolic complications in adolescents.

Environmental studies, metabolic research, and state of the art neurobiology point towards the reduced amount of natural day and sunlight exposure of the developing child’s organism as the consequence of increasingly long hours spent indoors online as the single unifying source of a whole set of health risks identified worldwide, as is made clear in this review of the current literature. Over exposure to digital environments, from abuse to addiction, now concerns even the youngest (ages 0 to 2), and triggers, as argued on the basis of clear examples herein, a chain of interdependent negative and potentially long-term metabolic changes. This leads to a deregulation of the serotonin and dopamine neurotransmitter pathways in the developing brain, currently associated with online activity abuse and/or internet addiction, and akin to that found in severe substance abuse syndromes. A general functional working model is proposed under the light of evidence brought to the forefront in this review.

Abstract: Astrocytes (ACs) are the most abundant human cell in the brain and importantly, are the master connecting and communicating cells that provide structural and functional support of brain cells at all levels of organization. Further, they are recognized to be the guardians and housekeepers of the brain. Protoplasmic perivascular astrocyte endfeet and their basal lamina form the delimiting outermost barrier (glia limitans) of the perivascular spaces in postcapillary venules and are important for the clearance of metabolic waste and comprise the glymphatic system, which is critically dependent on the proper waste removal by the pvACef polarized aquaporin 4 water channels. Also, the protoplasmic perisynaptic astrocyte endfeet (psACef) are important in cradling the neuronal synapses that serve to maintain homeostasis and serve a functional and supportive role for synaptic transmission. Enlarged perivascular spaces (EPVS) are emerging as important aberrant findings on magnetic resonance imaging (MRI) and associate with white matter hyperintensities, lacunes, aging, accepted to be biomarkers for cerebral small vessel disease, increased in obesity, metabolic syndrome, and type 2 diabetes. Knowledge is exponentially expanding regarding EPVS along with the glymphatic system, since EPVS are closely associated with impaired glymphatic function and waste removal from the brain to the cerebrospinal fluid and systemic circulation. This review intends to focus on how the pvACef play a crucial role in the development of EPVS.

In recent years, the interaction between adiponectin (APN), a versatile fat-associated adipokines, and eye disorders has become a captivating focus of interest. Unveiling the intricate relationship between APN and its receptors (AdipoRs) with aging eye disorders has emerged as a fascinating frontier in medical research. This review article delves into this captivating connection, illuminating the hidden influence of adipocytokine, APN on retinal health. This comprehensive review critically examines the latest findings and breakthroughs that underscore the pivotal roles of APN/AdipoRs signaling in maintaining ocular homeostasis and protecting against eye ailments. Here, we meticulously explore the intriguing mechanisms by which APN protein influences retinal function, lens clarity, and overall visual acuity. Drawing from an extensive array of cutting-edge studies, the article highlights APN's multifaceted functions, ranging from anti-inflammatory properties and oxidative stress reduction to angiogenic regulation within retinal and macula tissues. The involvement of APN/AdipoRs in mediating these effects opens up novel avenues for potential therapeutic interventions targeting prevalent aging eye conditions. Moreover, this review unravels the interplay between APN signaling pathways and age-related macular degeneration (AMD). The single-cell RNA seq results validate the expression of both the receptor isoform (AdipoR1/R2) in retinal cells. The transcriptomic analysis showed lower expression of AdipoR1/2 in dry AMD pathogenesis compared to healthy subjects. The inhibitory peptide (APN1) demonstrated over 75% suppression of CNV, whereas the control peptide did not exert any inhibitory effect on CNV. The elucidation of these relationships fosters a deeper under-standing of adipose tissue's profound influence on ocular health, presenting new prospects for personalized treatments and preventative measures. In conclusion, "Obesity Hormone's Role in Aging Eyes: Linking Adiponectin/AdipoRs to AMD" provides a captivating journey into the enthralling world of APN intertwining the realms of adipose biology and aged ophthalmology.

This study investigated the effects of whole-body circuit training using a weighted vest on plasma resistin, cardiovascular disease risk factors, and cardiorespiratory fitness for normal-weight obese women. In this study, thirty- six normal-weight obese women were divided into three groups: Weighted Vest Circuit Training (WVCT) (n = 12), Body Weight Circuit Training (BWCT) (n = 12), and Control (CON) (n = 12). Whole-body circuit training was conducted three times a week for eight weeks to compare and analyze plasma resistin, cardiovascular disease risk factors, and cardiorespiratory fitness before and after training. Although there was no significant baseline difference between the groups regarding skeletal muscle mass, it significantly increased for the WVCT group after eight weeks. percent body fat significantly decreased for the WVCT and BWCT groups, and there was a significant difference when the percent body fat of these two groups were compared to that of the control group. Moreover, the WVCT and BWCT groups displayed a significant decrease in plasma resistin, showing a significant difference from the CON group. The WVCT and BWCT group showed a significant decrease in plasma IL-6, whereas the CON group showed a significant increase. VO2max significantly increased post-training compared to before in the BWCT group and the WVCT group, and the WVCT group showed differences between groups compared to the BWCT group and the CON group. None of the three groups displayed significant changes in plasma hs-CRP, yet there was a significant difference between the hs-CRPs of the WVCT and BWCT group and that of the CON group. In conclusion, whole-body circuit training using a weighted vest efficiently improves body composition, plasma resistin, and cardiopulmonary fitness, reducing cardiovascular disease risk factors in normal-weight obese women.

Abstract: The marketing of Sugar-Sweetened Beverages (SSBs) within grocers is an obesogenic factor that negatively impacts children’s nutritional behavior, specifically regarding people from racial and ethnic minority groups. We aimed to develop and employ a methodology that more precisely assesses the availability, price, and promotion of SSBs to young immigrant children within independently owned grocery stores. A case comparison design was used to explore the differences in the grocery store landscape of SSB marketing by conducting an enhanced Nutrition Environment Measures Survey-SSB (NEMS-SSB) within 30 grocery stores in the Hispanic and Latino enclaves in Southwest Detroit, in the Arab and Chaldean enclaves in North-central Detroit, and in Warren, Hamtramck, and Dearborn, in comparison with 48 grocers in Metro Detroit. Organic, plant-based, and unsweetened toddler and infant beverages, as well as questions about marketing, were added to the original NEMS-S to capture the promotion tactics used in marketing SSBs. NEMS-SSB scores revealed in the immigrant enclaves there was a significantly higher availability of SSBs in grocery stores (−2.38), and they had lower prices than those in the comparison group (−0.52). Availability of unsweetened and organic beverages was zero in 97% of all participating grocery stores. Signage featuring cartoon characters was the most frequent in-store SSB marketing tactic. Widespread SSB marketing towards toddlers within the grocery stores in immigrant enclaves could be linked with the higher childhood obesity prevalence among this population. Our findings can assist local and national organizations in developing and implementing healthy eating interventions. This study can be repeated in other states to provide comparable results.

A recent review of global vitamin C status indicated a high prevalence of deficiency, particularly in low- and middle-income countries, as well as in specific subgroups within high-income countries. Here we provide a narrative of potential factors influencing vitamin C status. The in vivo status of vitamin C is primarily affected by dietary intake and supplement use. Dietary intake can be influenced by cultural aspects such as staple foods and traditional cooking practices. Environmental factors can also affect vitamin C intake and status; these include geographic region, season and climate, as well as pollution. Demographic factors such as sex, age, and race are known to affect vitamin C status, as do socioeconomic factors such as deprivation, education and social class, and institutionalization. Various health aspects affect vitamin C status; these include body weight, pregnancy and lactation, genetic variants, smoking, and disease states, including severe infections as well as various non-communicable diseases such as cardiovascular disease and cancer. Some of these factors have changed over time, therefore we also explore if vitamin C status has shown temporal changes. Overall, there are numerous factors that can affect vitamin C status to different extents in various regions of the world. Many of these factors are not taken into consideration during the setting of global recommended dietary intakes for vitamin C.

The investigation by the integrated approach newly introduced for this study indicates that insulin resistance (IR) would develop first preferentially in the muscle tissue with a relatively low cell turnover and then progress in sequence to the subcutaneous adipose tissue, to the visceral adipose tissue, and to the liver with higher cell turnovers. Moreover, metabolic disruptions due to IR vary widely from tissue to tissue, contrary to the conventional notion that IR merely impairs glucose uptake in the whole body. This warrants that IR be divided better into four distinct tissue specific IRs: muscle insulin resistance (MIR), subcutaneous adipose insulin resistance (s-AIR), visceral adipose insulin resistance (v-AIR), and hepatic insulin resistance (HIR). Tissue-specific IRs developing in the order of MIR, s-AIR, v-AIR, and HIR – producing tissue specific metabolic disruptions – would amount to nothing but the whole body insulin resistance (WBIR) evolving in four distinctively insulin resistant stages. The four stage metabolic evolution from rapid weight gain to visceral obesity to rapid weight loss to full blown diabetes not only complies well with the natural development history of diabetes but also resolves most of the controversies regarding obesity or diabetes, including visceral obesity, obesity paradox, and dawn phenomenon that have long remained metabolic puzzles. In addition, the four-stage WBIR evolution model refutes the entrenched notion of the lipid-induced insulin resistance (LIIR) but supports instead the glycation-induced insulin resistance (GIIR) proposed in this study. A speculation is that the glycation reaction activated ever more with WBIR evolving may serve as the common thread connecting each other a cluster of disorders or diseases that are often collectively referred to as the metabolic syndrome, such as obesity, diabetes, cardio/cerebral vasculopathy, nephropathy, neuropathy, and retinopathy.

Zn is an essential element for children related to optimal growth, development and nutritional metabolism. We measured Zn bioaccesibility (Zn-BA) levels of foods by Inductively coupled plasma mass spectrometry (ICP-MS) after in vitro digestion-fermentation method from children with gluten related disorders (GRD-CH), obesity (OB-CH) and allergy/intolerance to cow’s milk proteins (AICM-CH). Zn-BA levels in sick children (34.7 ± 28.8, 29.6 ± 30.1 and 26.7 ± 30.4%, respectively) were significantly lower (p &lt; 0.05) than in healthy norm-weight children (HE-CH). For AICM-CH, Zn-BA in animal foods was significantly lower than in plant foods, and in both plant and animal foods from sick and healthy children (p &lt; 0.05). In foods of animal origin in sick and healthy children, Zn-BA in foods heated in liquid media (frying and boiling) was significantly higher than in foods heated by hot air (roasting and grilling). In conclusion, in children the studied diseases diminished the Zn-BA, probably by the alteration of the gut microbiota which could negatively affect their appropriate long-term development. In AICM-CH, the allergy to cow's milk proteins could induce intestinal dysbiosis and inflammatory processes, leading to allergies to other animal food proteins, and to a more pronounced decrease of Zn-BA.

The comprehensive anabolic effects of insulin throughout the body, in addition to the control of glycemia, also include ensuring lipid homeostasis and anti-inflammatory modulation, especially in adipose tissue (AT). The prevalence of obesity, defined as a body mass index (BMI) ≥ 30 kg/m2, has been increasing worldwide on a pandemic scale with accompanying syndemic health problems, including glucose intolerance, insulin resistance (IR) and diabetes. Impaired tissue sensitivity to insulin or IR paradoxically leads to diseases with an inflammatory component despite hyperinsulinemia. Therefore, an excess of visceral AT in obesity initiates chronic low-grade inflammatory conditions that interfere with insulin signaling via insulin receptor (INSR). Moreover, in response to IR, hyperglycemia itself stimulates a primarily defensive inflammatory response associated with the subsequent release of numerous inflammatory cytokines and a real threat of organ function deterioration. In this review, all components of this vicious cycle are characterized with particular emphasis on the interplay between insulin signaling and both the innate and adaptive immune responses related to obesity. Increased visceral AT accumulation in obesity should be considered the main environmental factor responsible for the disruption in the epigenetic regulatory mechanisms in the immune system, resulting in autoimmunity and inflammation.

Thyroid hormones, their metabolites and synthetic analogues are potential anti-steatotic drug candidates considering that subclinical and manifest hypothyroidism is associated with hepatic lipid accumulation, non-alcoholic fatty liver disease, and its pandemic sequelae. Thyromimetically active compounds stimulate hepatic lipogenesis, fatty acid beta-oxidation, cholesterol metabolism and metabolic pathways of glucose homeostasis. Many of these effects are mediated by T3 receptor β1-dependent modulation of transcription. However, rapid non-canonical mitochondrial effects have also been reported, especially for the metabolite 3,5-diiodothyronine (3,5-T2), which does not elicit the full spectrum of “thyromimetic” actions inherent to T3. Most preclinical studies in rodent models of obesity and first human clinical trials are promising with respect to the antisteatotic hepatic effects, but potent agents exhibit unwanted thyromimetic effects on the heart and/or suppress feedback regulation of the hypothalamus-pituitary-thyroid-periphery axis and the fine-tuned thyroid hormone system. This review focusses on 3,5-T2 effects on hepatic lipid and glucose metabolism and (non-)canonical mechanisms of action including its mitochondrial targets. Various high fat diet animal models with distinct thyroid hormone status indicate species- and dose-dependent efficiency of 3,5-T2 and its synthetic analogue TRC150094. No convincing evidence has been presented for their clinical use in prevention or treatment of obesity and related metabolic conditions.

Obesity-associated metabolic abnormalities comprise of a cluster of conditions including dyslipidemia, insulin resistance, diabetes, and cardiovascular diseases that has affected more than 650 million people all over the globe. Obesity results from accumulation of white adipose tissues mainly due to the chronic imbalance of energy intake and energy expenditure. Variety of approaches to treat or prevent obesity, including lifestyle interventions, surgical weight loss procedures and pharmacological approaches to reduce energy intake and increase energy expenditure have failed to substantially decrease the prevalence of obesity. Brown adipose tissue (BAT), the primary source of thermogenesis in infants and small mammals may represent a promising therapeutic target to treat obesity by promoting energy expenditure through non-shivering thermogenesis mediated by mitochondrial uncoupling protein 1 (UCP1). Since the confirmation of functional BAT in adult humans by several groups, approximately a decade ago and its association with a favorable metabolic phenotype, intense interest on the significance of BAT in adult human physiology and metabolic health has emerged within the scientific community to explore its therapeutic potential for the treatment of obesity and metabolic diseases. Substantially decreased BAT activity in individuals with obesity indicates a role for BAT in setting of human obesity. On the other hand, BAT mass and its prevalence has been reported to correlate with lower body mass index (BMI), decreased age and glucose levels, leading to lower incidence of cardio metabolic diseases. Increased cold exposure in adult humans with undetectable BAT was associated with decreased body fat mass and increased insulin sensitivity. Deeper understanding of the role of BAT in human metabolic health and its inter-relationship with body fat distribution and deciphering proper strategies to increase energy expenditure by either increasing functional BAT mass, or inducing white adipose browning holds the promise for possible therapeutic avenues for the treatment of obesity and associated metabolic disorders.

Psoriasis is nowadays recognized as a multifactorial systemic disease with complex and still not fully understood pathogenesis. In psoriatic patients the increased cardiovascular disease (CVD) risk and frequent comorbidities like obesity are observed. The aim of this study was to investigate differences in miRNA (miR-22-3p, miR-133a-3p, miR-146a-5p, miR-369-3p and Let-7b-5p) involved in CVD risk among psoriatic patients with overweight/obesity and with normal weight. The study comprised 28 male psoriatic patients and 16 male healthy controls. miRNA isolated from peripheral blood mononuclear cells was reverse-transcribed and RT-qPCR was performed. We have found the decreased levels of miR-22, miR-133a, miR-146a, and miR-369 among the psoriatic patients. There was a statistically significant difference in miR-22 and miR-146a levels between psoriatic patients with overweight/obesity and with normal weight. There were positive correlations between miR-22 and miR-146a levels and psoriatic arthritis (PsA) in psoriatic patients with normal weight and between miR-133a level and PsA in the overweight/obese patients. The decreased levels of selected miRNA are consistent with their levels observed in CVD indicating their impact in the CVD risk in psoriatic patients. miR-22 and miR-146 may be recognized as one of the contributing factors in the obesity-CVD-psoriasis network.

Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer’s disease-dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is associated with cognitive impairments associated with metabolic factors and increases the cellular vulnerability to develop the age-related increased risk of LOAD. This review addresses possible mechanisms due to obesity, aging, multiple intersections between T2DM and LOAD and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic db/db models are utilized to demonstrate marked cellular remodeling changes of mural and glia cells and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain’s neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. aging (chronic age-related diseases); ii. metabolic (hyperglycemia - advanced glycation end-products and its receptor (AGE/RAGE) interactions and hyperinsulinemia – insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen-nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis - vascular stiffening and microvascular NVU/neuroglial remodeling) with resulting impaired cerebral blood flow.

Posttraumatic stress disorder (PTSD) and/or specific PTSD symptoms may evoke disordered eating and unhealthy lifestyles, resulting in adverse cardiometabolic events (e.g., hypertension and obesity) in certain groups, which may implicate the treatment of this complex condition. The diagnostic criteria of PTSD have lately expanded beyond the three common symptoms (intrusion, avoidance, and hyperarousal). Simultaneously, four-, five-, and six-dimensional structures of the Impact of Event Scale-Revised (IES-R), a popular PTSD measure, seem to be more robust than the original three-dimension structure. Within the context of COVID-19, this instrumental study used a convenience sample of 58 dental healthcare workers (HCWs) from Russia (mean age = 44.1±12.2 years, 82.8% females) to examine the criterion and predictive validity of two IES-R structures: the IES-R3 and the IES-R6 (with the added symptoms of numbing, sleep disturbance, and irritability). The subscales of the two IES-R structures expressed good internal consistency, strong correlations with the PTSD Symptom Scale (PSS), hypertension diagnosis, and high body mass index (BMI). In receiver-operating characteristic (ROC) curve analysis, all IES-R models perfectly predicted the PSS (all area under the curve (AUC) >0.9, p values <0.001). The IES-R, both hyperarousal subscales, and the IES-R3 intrusion subscale significantly predicted high BMI. Both avoidance subscales and the IES-R3 intrusion subscale, not the IES-R, significantly predicted hypertension. In conclusion, both IES-R structures can reliably measure PTSD symptoms. The IES-R, hyperarousal, and intrusion may be credible criterion variables for predicting high BMI within PTSD while the intrusion and avoidance subscales may reflect the cardiovascular consequences associated with PTSD more reliably than the IES-R itself. The IES-R subscales may predict cardiometabolic adversities in PTSD, signifying a need for proper assessment of lifestyle and the application of dietary and exercise interventions in order to lower physical morbidity in PTSD. Replicating the study in larger samples, which comprise different physical and mental conditions from heterogenous cultural contexts is pivotal to validate the results (e.g., in specific groups such as those with confirmed traumatic exposure and comorbid mood dysfunction).

Platelets have long been associated with sustaining the balance between hemostasis and thrombosis. Platelets, however, are also involved in a wide range of biological activities, including inflammation, immunology, wound healing, cancer biology, and angiogenesis. Platelets' diverse roles are mediated by the expression of various adhesive and immune receptors and the secretion of a diverse array of bioactive proteins, ions stored in granules, and several lipid mediators. Platelets also release pro-inflammatory and anti-inflammatory, and angiogenic factors and shed microparticles into the bloodstream. The challenge for therapeutic intervention in non-hemostatic disease is identifying the factors that primarily inhibit specific targets implicated in platelets' complicated contribution to inflammation or tumor growth while leaving their hemostatic function intact. In addition, blood platelets are involved in infection and innate and adaptive immunity by mediating complicated vascular homeostasis via specialized receptors and granule release, RNA transfer, and mitochondrial secretion. Anti-platelet drugs/bioactive compounds are developed based on their platelet anti-aggregatory properties; however, very little information is available on their effects on non-hemostatic function. Therefore, a better understanding of the impact of the anti-platelet bioactive on the platelets' diverse roles and mechanisms may help develop new strategies and prevent CVD and other diseases. In this review, a comprehensive overview of platelet multifunctional roles in CVD and other diseases and dietary factors' modulatory effects are described.