Hyperlipidemia is the fat particles excess in the serum. Hyperlipidemia increases the mortality rate that occurs with other metabolic disorders. Hyperlipidemia is classified into familial and acquired subgroups. Moreover, Hyperlipidemia etiology is based on environmental or genetic factors. For instance, abnormal HMG-CoA regulation down-regulates ubiquitin ligase and targets variable oxidative stress-related condition proteins. There has been proven reactive oxygen species (ROS) overshoot happens during hyperlipidemia occurrence. OS, directly and indirectly, regulates molecular cascades within the cell and leads to gene expression alteration. At this molecular juncture, AMPK is affected by ROS. AMPK is a serine-threonine kinase and a critical energy balance. Low energy conditions result in AMPK activation due to the down-regulation of protein and lipid synthesis. Furthermore, ER stress and activated unfolded protein proteasomal response and autophagy are AMPK mediated. Polyphenols are widespread dietary plant-based compounds that regulate gene expression and signal conduction. Through the hyperlipidemic state, FFAs releasing indirectly connect to AMPK/NF-κB pathway then polyphenols target them. AMPK, during this FFA exposure, down-regulates de novo lipid molecules generation. Likewise, if AMPK/mTOR pathway failure is prolonged, the hyperlipidemic state may be explicit, activated by natural herbal mediators, e.g., polyphenols. Polyphenols activate the AMPK signaling pathway and influence lipid metabolism. Polyphenol-mediated AMPK activation results in lipogenesis inhibition and lipophagy. Cholesterol efflux mediated polyphenols lipid-lowering effects, accessing LXR pathway. All these clues persist on direct or indirect AMPK-related polyphenolic anti-hyperlipidemic effects.

The determination of a causal relationship between gut microbiota and a range of dyslipidemia remains uncertain. To clarify these associations, we employed a two-sample mendelian randomization (MR) analysis utilizing the inverse-variance weighted (IVW) method. This comprehensive analysis investigated the genetic variants that exhibited a significant association (p<1e-5) with 129 distinct gut microbiota genera, and their potential link to diverse forms of dyslipidemia. The results indicated a potential causal relationship between 22 gut microbiota genera and dyslipidemia in humans. Furthermore, these findings suggested that the impact of gut microbiota on dyslipidemia regulation is dependent on the specific phylum, family, and genus. Bacillota phylum demonstrated the greatest diversity, with 15 distinct genera distributed among 8 families. Notably, gut microbiota derived from the Lachnospiraceae and Lactobacillaceae families exhibit statistically significant associations with lipid levels that contribute to overall health (p<0.05). The sensitivity analysis indicated that our findings possess robustness (p>0.05). The findings of our investigation provide compelling evidence that supports a causal relationship between the gut microbiota and dyslipidemia in the human body. It is noteworthy to highlight the significant influence of the Bacillota phylum as a pivotal regulator of lipid levels, and the families Lachnospiraceae and Lactobacillaceae should be acknowledged as probiotics that make substantial contributions to this metabolic process.

Atherogenesis and dyslipidemia increase the risk of cardiovascular disease, which is the leading cause of death in developed countries. While blood lipid levels have been studied as disease predictors, their accuracy in predicting cardiovascular risk is limited due to its high interindividual and interpopulation variability. The lipid ratios: atherogenic index of plasma (AIP=log TG/HDL-C) and the Castelli risk index 2 (CI2=LDL-C/HDL-C) have been proposed as better predictors of cardiovascular risk, but the genetic variability associated to these ratios has not been investigated. This study aimed to identify genetic associations with these indexes. The study population (n=426) included males (40%) and females (60%) aged 18-52 years (mean 39 years), the Infinium GSA array was used for genotyping. Regression models were developed using R and PLINK. AIP was associated with variation on APOC3, KCND3, CYBA, CCDC141/TTN, and ARRB1 (p-value < 2.1E-6) the three former previously associated to blood lipids, while CI2 was associated with variants on DIPK2B, LIPC, and 10q21.3 rs11251177 (p-value 1.1E-7) the latter previously linked to coronary atherosclerosis and hypertension. KCND3 rs6703437 was associated with both indexes. This study is the first to characterize the potential link between genetic variation and atherogenic indexes, AIP and CI2, highlighting the relation between genetic variation and dyslipidemia predictors. These results also contribute to consolidating the genetics of blood lipid and lipid indexes.

Metabolic syndrome (MetS) refers to the group of several interconnected risk factors that collectively double the risk of cardiovascular disease. Epilepsy is linked to MetS across all age groups, though its prevalence differs across various studies. This can be understood from the perspective of seizure-related metabolic abnormalities, long-term antiepileptic drugs (AEDs) use, and a more sedentary lifestyle due to epilepsy. The factors that are considered in developing MetS for patients with epilepsy (PWE) are age, residence, level of physical activity, food intake status, epilepsy subtype, epilepsy duration, current (AEDs) use, drug responsiveness status, body-mass index (BMI), total cholesterol and LDL-cholesterol levels. A deeper understanding of the epilepsy-AED-MetS connection and the exploration of lifestyle interventions hold the promise of significantly improving the overall health and well-being of PWE. Clinicians managing PWE should closely monitor various risk factors for developing MetS and consider them when selecting AED treatment.

The production and secretion of very-low density lipoproteins (VLDL) by hepatocytes has a direct impact on liver fat content as well as the concentration of cholesterol and triglycerides in the circulation and thus affects liver and cardiovascular health, respectively. Importantly, excess caloric intake and lack of physical activity are associated with overproduction of VLDL, hepatic steatosis, and increased levels of atherogenic lipoproteins. Cholesterol as well as triglycerides in remnant particles after VLDL lipolysis are risk factors for atherosclerotic cardiovascular disease (ASCVD) and have garnered increasing attention over the last few decades. To date, however, increased risk of ASCVD is not the only concern when considering today’s cardiometabolic patients, as they often also suffer from hepatic steatosis. This notion highlights the importance of understanding the molecular regulation of VLDL biogenesis. Fortunately, there has been a resurgence of interest in the intracellular assembly, trafficking, degradation, and secretion of VLDL by hepatocytes, that has led to many exciting new molecular insights, the topic of this review. We think that increasing our understanding of the biology of this pathway will help improve the health of the cardiometabolic patient in the long term.

The effect of Gymnema Sylvestre supplementation on beta cell and hepatic activity was explored in an alloxan-induced hyperglycemic rat model. Adult rats were made hyperglycemic via a single inj. (i.p) of Alloxan (120mg/kg b.w). Gymnema Sylvestre was supplemented @250mg/kg and 500mg/kg b.w. Blood glucose levels were constantly monitored. After 21 days, rats were euthanized, and blood and tissues (pancreas and liver) were collected for biochemical, expression, and histological analysis. One-way ANOVA was used to compare the means of different treatment groups. Gymnema Sylvestre significantly reduced blood glucose levels with a subsequent increase in plasma insulin levels in a dosage-dependent manner. Total oxidant status (TOS), malondialdehyde, LDL, VLDL, ALT, AST, triglyceride, total cholesterol, total protein, C-reactive protein, and cortisol levels were reduced significantly in alloxan-treated hyperglycemic rats supplemented with Gymnema Sylvestre as compared to control. Significantly raised paraoxonase, arylesterase, albumin, and HDL levels were also observed in Gymnema Sylvestre supplemented hyperglycemic rats. Increased mRNA expression of Ins-1, Ins-2, Gck, Pdx1, Mafa, and Pax6 were observed, while decreased expression of Cat, Sod1, Nrf2, and NF-kB was observed in the pancreas. Whereas increased mRNA expression of Gck, Irs1, SREBP1c, and Foxk1 and decreased expression of Irs2, ChREBP, Foxo1, and FoxA2 were observed in the liver. The current study indicates the potent effect of Gymnema Sylvestre on the transcription modulation of the insulin gene in the alloxan-induced hyperglycemic rat model. Enhanced plasma insulin levels further help to improve hyperglycemia-induced dyslipidemia through transcriptional modulation of hepatocytes.

Background The metabolic syndrome increases the risk of developing various systemic cancers. The prevalence of the metabolic syndrome in newly diagnosed glioblastoma patients is unknown. Further, there have been contradictory reports about how the metabolic syndrome affects clinical outcomes. Therefore, the purpose of this study is to test the hypothesis that the metabolic syndrome is associ-ated with increased prevalence of glioblastoma and worsened survival outcomes. Methods This retrospective cohort study examines seventy-three patients with isocitrate dehydrogenase (IDH)-wild type glioblastoma as it provides for a relatively homogeneous population to examine. Patient characteristics, vital signs, lab results, tumor molecular markers, and overall survival were analyzed. Patients with the metabolic syndrome and individual risk factors were identified and survival outcomes were examined. Results Our results demonstrate that there is a higher prevalence of the metabolic syndrome in our cohort of patients with glioblastoma than the general population (41% vs 33%). We also demonstrate that after correction for confounding variables, the metabolic syndrome is not significantly asso-ciated with overall survival (p = 0.1). When analyzing individual metabolic risk factors, we demonstrate that there is a significant association between the accumulation of metabolic risk factors and decreased survival (p = 0.03), and hyperglycemia emerges as a significant independent risk factor for decreased survival (p = 0.05). Conclusion These results suggest that metabolic risk factors can affect survival in patients with glioblastoma, which can have significant implications for clinical practice. These findings need to be further ex-plored through further clinical and mechanistic studies.

Background: Recent studies suggest an association between long-term air pollution, diet, and health outcomes, but there are limited studies on how short-term air pollution affects dyslipidemia in particular. We aimed to investigate this association with modified fruit and vegetable consumption.Methods: The Cardiovascular Disease Association Study (CAVAS) included 8,779 participants between 2007 and 2016. Particulate matter (PM_2.5) and nitrogen dioxide (NO₂) levels were estimated using community multiscale air quality models. Short-term air pollution exposure was defined as a moving average over a lag time from “lag 1 days” to “lag 14 days.” Fruit and vegetable intake was categorized into 'total vegetables (TV),’ 'non-salted vegetables (NSV),' 'salted vegetables (SV),' 'fruits (F),' 'non-salted vegetables + fruits (NSVF),' and 'total vegetables + fruits (TVF).' Dyslipidemia was defined by total cholesterol ≥240 mg/dl, LDL cholesterol ≥160 mg/dl, HDL cholesterol <40 mg/dl, serum triglycerides ≥200 mg/dl, or physician-reported dyslipidemia.Results: Higher short-term PM_2.5 concentrations were associated with an increased risk of dyslipidemia (odds ratio (OR) = 1.012, 95% CI: 1.003, 1.020 for a lag of 14 days). High PM_2.5 groups (≥23.3 μg/m³) with a higher TV intake (≥186.1 g/day) were associated with a decreased risk of dyslipidemia (OR = 0.88, 95% CI: 0.78, 0.99). Additionally, high PM_2.5 groups (≥23.3 μg/m³) with a higher intake of SV (≥110.6 g/day) were associated with a decreased risk of dyslipidemia (OR = 0.86, 95% CI: 0.76, 0.97). Conclusion: Our study suggests that vegetable consumption is an important dietary factor for attenuating risk of dyslipidemia associated with short-term air pollution exposure.

Background: Subclinical myocardial injury (SCMI) is associated with an increased risk of poor cardiovascular disease (CVD) outcomes. Understanding the underlying risk factors for SCMI is crucial for the prevention and management of CVD. We hypothesized that atherogenic dyslipidemia, a combination of high triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C), is associated with an increased risk of SCMI. Methods: This analysis from the third National Health and Nutrition Examination Survey (NHANES-III) included 7,093 participants (age 59.3±13.4 years, 52.8% women, and 49.4% White) free of CVD. Atherogenic dyslipidemia was defined as TG ≥150 mg/dL and HDL-C <40 mg/dL in men or <50 mg/dL in women. A validated electrocardiographic-based cardiac infarction injury score (CIIS) ≥10 was considered positive for SCMI. Multivariable logistic regression analysis was used to examine the association of different combinations of TG and HDL-C groups, including atherogenic dyslipidemia with SCMI. Results: About 22.5% (n=1,594) of participants had atherogenic dyslipidemia, and 26.3% (n=1862) had SCMI. Compared to participants with normal TG and normal HDL-C, those with atherogenic dyslipidemia had a higher prevalence of SCMI (31.2% vs. 23.9%, p-value <0.001). In a multivariable logistic regression model, atherogenic dyslipidemia was associated with the highest odds of SCMI followed by high TG/normal HDL-C, then low HDL-C/normal TG [OR (95% CI): 131 (1.14,1.52), 1.13 (0.97,1.33), and 1.01(0.86,1.20), respectively). Conclusions: Atherogenic dyslipidemia is associated with a higher risk of SCMI, which highlights the role of nontraditional risk factors in the development of subclinical CVD.

Introduction Currently, the increase in the percentage of obese people observed along with the development of civilization, reaching the level of a global pandemic, has forced the search for methods of effective and permanent obesity treatment. Obesity is a multifactorial disease, it coexists with many disease entities and requires multidisciplinary treatment. Obesity leads to metabolic changes in the form of metabolic syndrome, which includes, among others, atherogenic dyslipidemia. The proven relationship between dyslipidemia and cardiovascular risk enforces the need to effectively improve the lipid profile of obese patients. Laparoscopic sleeve gastrectomy is a method of surgical treatment of morbid obesity which improves bariatric and metabolic parameters. The aim of the study was to assess the effectiveness of laparoscopic sleeve gastrectomy (LSG) in improving lipid profile parameters in 1-year follow-up. Material and Methods Bariatric parameters of 196 patients who underwent laparoscopic sleeve gastrectomy as well as lipid profile of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-NDL, and triglycerides (TG) in 1-year observation were analyzed. Results Improvements in bariatric parameters were observed in patients after LSG. Total cholesterol, low-density lipoprotein (LDL), triglycerides and non-HDL levels decrease were observed along with the increase of high-density lipoprotein (HDL) cholesterol level. Conclusions Sleeve gastrectomy is an effective method of treating obesity and improving the lipid profile in obese patients.

Background: Chronic kidney disease (CKD) is a significant cardiovascular (CV) risk factor, with dialysis-dependent CKD (DD-CKD) patients facing high mortality rates. Hypercholesterolemia is another crucial CV risk factor, typically managed with lipid-lowering therapy, though its efficacy in DD-CKD remains uncertain. Evidence shows mixed results regarding the benefits of statins in these patients. Citrate-based dialysates are known to reduce inflammatory biomarkers compared to acetate-based ones, potentially impacting lipid profiles and immune responses. This study aimed to determine the effects of citrate versus acetate dialysate on lipid profiles and immunophenotypes in DD-CKD patients. Methods: This unicentric, cross-over, prospective study included 21 hemodialysis patients (10 males, 11 females, average age 62.25 years). Each patient underwent 24 dialysis sessions (12 with each dialysate) and acted as their own control. Lipid profiles, immunological parameters, and nutritional and inflammatory markers were measured before the last session with each dialysate. Results: Compared to acetate dialysate (AD), citrate dialysate (CD) resulted in significantly higher LDL (75.71 vs. 67.05 mg/dL, p=0.042) and HDL (51.19 vs. 47.14 mg/dL, p=0.013), and lower TG (97.86 vs. 110.38 mg/dL, p=0.046). CD also led to higher NK cells (19.24 vs. 16.95%, p=0.035), higher complement C3 levels (115.14 vs. 107.81 mg/dL, p=0.009) and lower CD3+ CD8+ and CD16+56+ lymphocytes. Finally, total lymphocytes were lower with AD than with CD. We found no difference in predialysis nutritional nor inflammatory parameters (IL-6 and hs-CRP) except for ESR, which was higher when subjects used CD than AD. Conclusion: There are significant differences in lipid and immunophenotypic profiles that should increase the CV risk of patients who use CD. However, numerous studies have shown no differences, or even a benefit in mortality in certain HD subpopulations that use CD. Further studies are needed to understand if the observed changes may be counterbalanced by other mechanisms potentially provided by citrate (e.g., reducing vascular calcification).

Infection with human immunodeficiency virus (HIV) and induced acquired immune deficiency syndrome (AIDS) represent one of the greatest health burdens worldwide. The complex pathophysiological pathways that link highly active antiretroviral therapy (HAART) and HIV infection per se with dyslipidemia make the management of lipid disorders and the subsequent increase in cardiovascular risk essential for the treatment of people living with HIV (PLHIV). Amongst the HAART regimens, darunavir and atazanavir in terms of protease inhibitors, tenofovir disoproxil fumarate, nevirapine or rilpivirine in terms of nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors respectively, and especially integrase inhibitors, have demonstrated the most favorable lipid profile emerging as sustainable options in HAART substitution. To this day, statins remain the cornerstone pharmacotherapy for dyslipidemia in PLHIV, although important drug-drug interactions with different HAART agents should be taken into account upon treatment initiation. For those intolerant or not meeting therapeutic goals, the addition of ezetimibe, PCSK9, bempedoic acid, fibrates or fish oils should also be considered. This review summarizes the current literature on the multifactorial etiology and intricate pathophysiology of hyperlipidemia in PLHIV, with an emphasis on the role of different HAART agents, while also providing valuable insights into potential switching strategies and therapeutic options.

Evinacumab, a human monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3), has recently been approved by U.S. Food and Drug Administration as an add-on therapy for homozygous familial hypercholesterolemia (HoFH) in patients of 12 years and older. Its role as a triglyceride-lowering drug is also emerging in the literature. However, it has not been approved for this indication yet, neither in the adult nor in the pediatric population. We describe the case of a 10-year-old boy who underwent an allogeneic hematopoietic stem cell transplant for acute lymphoblastic leukemia complicated by chronic graft–versus–host disease (GVHD) and presented life-threatening refractory hypertriglyceridemia due to the concomitant use of ruxolitinib and sirolimus. After the failure of the insulin treatment and due to the technical impossibility of performing lipid apheresis, we underwent the child to evinacumab treatment, obtaining a dramatic rapid reduction in triglyceride and cholesterol levels. This is the first report of a pediatric patient younger than 12 years in Europa receiving evinacumab to treat severe hypertriglyceridemia. The therapy with angiopoietin-like proteins inhibitors has been effective, safe, and well-tolerated in our patient, suggesting that evinacumab may be used in the pediatric population when other therapeutic strategies are ineffective or contraindicated.

There is evidence that behavioral risk factors such as western type diet, and life style can predispose to oxidative stress, deficiency in antioxidant status, hyperglycemia, dyslipidemia and increase in inflammation in tissues of various organs: beta cells of the pancreas, LDL receptors in the hepatocytes, endothelium, neurons, osteocytes and gut. Further studies indicate that diets rich in antioxidant flavonoids, omega-3 fatty acids and fiber in foods were inversely associated whereas western-type foods were positively associated with risk of mortality due to cardiovascular diseases (CVDs). One important cause for beneficial effects of diet may be certain foods and nutrients such as vegetables, fruits and whole grains that are rich in fiber and flavonoids, known to produce liters og molecular hydrogen in the gut. It seems that, high-fiber diets, prebiotic and probiotics can produce greater hydrogen, which acts as an antioxidant and may inhibit free radical generation. Recent studies indicate that molecular hydrogen can inhibit hydroxyl and nitrosyl radicals and can directly act as antioxidant in the cells and tissues, which can cause marked decline in oxidative stress and inflammation leading to significant decline in CVDs and metabolic diseases. Clinical and experimental studies indicate that hydrogen therapy such as hydrogen rich water can provide benefits in the management of CVDs and metabolic diseases. Larger studies are necessary to verify the role of hydrogen administration in CVDs.

Diabetes is a major risk factor for tuberculosis (TB). Diabetes increases the risk of progression from latent tuberculosis infection (LTBI) to active pulmonary TB and TB patients with diabetes are at greater risk of more severe disease and adverse TB treatment outcomes compared to TB patients without co-morbidities. Diabetes is a complex disease characterized not only by hyperglycemia but also various forms of dyslipidemia. However, the relative contribution of these underlying metabolic factors to increased susceptibility to TB are poorly understood. This review summarizes our current knowledge on epidemiology and clinical manifestation of TB and diabetes comorbidity. We subsequently dissect the relative contribution of body mass index, hyperglycemia, elevated cholesterol and triglycerides on TB disease severity and treatment outcomes. Lastly, we discuss the impact of selected glucose and cholesterol lowering treatments frequently used in the management of diabetes on TB treatment outcomes.

Although vitamin D deficiency has been correlated with an increased risk of cardiovascular disease (CVD), there are few data on the association between 25-hydroxyvitamin D (25(OH) D) and atherogenic indices predictive of CVD. This study aimed to investigate the relationship of vitamin D status with lipid profile and atherogenic indices in adult women in Morocco. Three hundred healthy women, aged 18 to 50 years, from Meknes were included. Fasting 25(OH) D and lipid concentrations were determined using a one-step electrochemiluminescence-based immunoassay and an enzymatic method, respectively. Atherogenic indices (Atherogenic index of plasma (AIP), non-HDL cholesterol (Non-HDL-C), Atherogenic coefficient (AC), Castelli risk indices I and II (CRI-I and II), and CHOLIndex (CI)) were calculated using conventional lipid parameters. Logistic regression models and operating characteristic curve (ROC) analysis were used to assess the relationship of the variables and estimate the threshold of 25(OH) D levels associated with high atherogenic indices. 25(OH) D below 20 ng/ml was significantly associated with an enhanced risk of hypertriglyceridemia and elevated values of AIP, AC, Non-HDL-C, and CRI-I with an OR (95% CI) of 4.904 (1.856-12.959); 3.637(2.149-6.158); 3.589(1.673-7.700); 2.074(1.215-3.540), and 2.481(1.481-4.123), respectively. According to ROC analysis, the likelihood of hypertriglyceridemia and high values of AIP, AC, Non-HDL-C, and CRI-I were associated with 25(OH)D thresholds ≤15.15 ng/ml, ≤ 17.5 ng/ml, ≤ 19.8 ng/ml, ≤ 20.1 ng/ml and ≤ 19.5 ng/ml, respectively, all p &lt; 0.01. Based on atherogenic indices, this study indicates that vitamin D below 20 ng/ml may increase the risk of cardiovascular disease in adult women. Additional health efforts are needed to raise awareness among women and healthcare providers in preventing and controlling cardiovascular risk factors.

INTRODUCTION: Cardiovascular prevention is less effective than expected due to the concern about polymedication of professionals and the lack of adherence of patients. Polypills are presented as a possible solution, increasing therapeutic adherence in the medium or long term and improving therapeutic results compared to the administration of drugs separately: they increase effectiveness and Adherence of patients to primary and secondary cardiovascular prevention programs, without increasing the cost of the intervention. OBJECTIVES: Study #Trigeria: to specify the combined prevalence of Atrial Fibrillation, Dyslipidemia and Hypertension and analyze the pharmacological prescription for these pathologies and the possible indications and advantages that would have the prescription of a polypill for these risk factors.METHODS: Observational analytical study on the pathological history in elderly institutionalized in nursing homes and analysis of prescribed oral medication.RESULTS: 169 people analyzed (79.3% women) from 4 nursing homes; 8.9% had a history of Atrial Fibrillation, Dyslipidemia and Arterial Hypertension; these had a higher prevalence of heart disease (42.9%) and Cerebral Vascular Accident (35.7%). Polymedication was present in 88.5%, with an average of 6.94 oral drugs prescribed; among those with the three pathological antecedents, the average number of oral medications was 8.60. Only 26.7% of those with all three factors were prescribed drugs to control them.DISCUSSION: There are high rates of polymedication in the sample and low rates of prescription of antiplatelet agents in people with Atrial Fibrillation (26.5%); the low prescription of statins and antihypertensives of the ACE inhibitor or ARB-II groups may be due to good control with non-pharmacological measures or by the use of other groups of drugs . A polypill holding the drugs that control the three factors studied could increase the prescription rate while simplifying the administration schedule and reducing polymedication by 23.25% improving prescription, increasing adherence and control of risk factors without increasing pharmaceutical expenditure.CONCLUSIONS: There is a low rate of prescription of antiplatelet agents among people with atrial fibrillation. Combination methods (polypills) can increase the suitability of prescriptions in people with polypathology, improving prescribing, simplifying administration and increasing adherence to pharmacological treatments.

Animal studies have shown that developmental exposures to polybrominated diphenyl ethers (PBDE) permanently affect blood/liver balance of lipids. No human study has evaluated associations between in utero exposures to persistent organic pollutants (POPs) and later life lipid metabolism. In this pilot, maternal plasma levels of PBDEs (BDE-47, BDE-99, BDE-100, and BDE-153) and polychlorinated biphenyls (PCB-138, PCB-153, and PCB-180) were determined at delivery in participants of GESTation and Environment (GESTE) cohort. Total cholesterol (TCh), triglycerides (TG), low and high density lipoproteins (LDL-C and HDL-C), total lipids (TL), and PBDEs were determined in serum of 147 children at ages 6-7. General linear regression was used to estimate the relationship between maternal POPs and child lipid levels with adjustment for potential confounders, and adjustment for childhood POPs. In utero BDE-99 was associated with lower childhood levels of TG (p=0.003), and non-significantly with HDL-C (p=0.06) and TL (p=0.07). Maternal PCB-138 was associated with lower childhood levels of TG (p=0.04), LDL-C (p=0.04), and TL (p=0.02). Our data indicate that in-utero exposures to POPs may be associated with long-lasting decrease in circulating lipids in children, suggesting increased lipid accumulation in the liver, a mechanism involved in NAFLD development, consistent with previously reported animal data.

This study aimed to investigate the prevalence of cardiovascular disease (CVD) risk factors among Algerian aircrew, a population exposed to unique environmental and occupational stressors. By comparing these rates to the general population, we sought to identify specific health challenges faced by aircrew. Methods: A cross-sectional study was conducted on 154 Algerian aircrew participants. Prevalence rates for current smoking, hypertension, diabetes, and dyslipidemia were compared between the aircrew and a general population control group. Results: Our findings revealed significantly higher rates of current smoking among aircrew compared to the general population. Additionally, smoking, dyslipidemia, hypertension, and diabetes emerged as the most prevalent risk factors within the aircrew population. Conclusions: Despite the rigorous selection process for aircrew recruitment, our study confirms findings from previous literature, highlighting the high rate of normal qualifying examinations. The substantial sample size and homogeneous nature of the aircrew population enhance the reliability and generalizability of our conclusions. These findings underscore the importance of targeted interventions to mitigate CVD risk factors within this specific population, given the unique environmental and occupational factors associated with aircrew.

Ozonated sunflower oil (OSO) is renowned for its diverse therapeutic benefits. Nonetheless, the consequences of extended dietary intake of OSO have yet to be thoroughly investigated. Herein, the effect of 2-year dietary supplementation of OSO was examined on the zebrafish survivability, obesity, skeletal deformities, swimming behavior, and liver, kidney, ovary, and testis function. Results showed that the zebrafish feed supplemented with 20% (wt/wt) OSO for 2 years emerged with higher survivability and body weight management compared to sunflower oil (SO) and normal diet (ND) supplemented zebrafish. Radio imaging (X-ray) based analysis revealed 2.6o and 15.2o lower spinal curvature in the OSO-supplemented groups than in SO and ND-supplemented groups; consistently, OSO-supplemented zebrafish showed better swimming behavior. The histology analysis of the liver revealed a least fatty liver change and interleukin 6 (IL-6) generation in the OSO-supplemented group. Additionally, a significantly lower level of reactive oxygen species (ROS), apoptotic, and senescent cells were observed in the liver of the OSO-supplemented zebrafish. Also, no adverse effect on the kidney, testis, and ovary morphology was detected during 2 years of OSO consumption. Moreover, lower senescence with diminished ROS and apoptosis was noticed in the kidney and ovary in response to OSO consumption. The OSO supplementation was found to be effective in countering age-associated dyslipidemia by alleviating total cholesterol (TC), triglycerides (TG), low-density lipoproteins (LDL-C) and elevating high-density lipoproteins (HDL-C)/TC levels. Conclusively, prolonged OSO consumption showed no adverse effect on the morphology and functionality of vital organs; in fact, OSO supplementation displayed a protective effect against age-associated detrimental effects on spinal deformities, vital organ functionality, cell senescence, and survivability of zebrafish.

Sulfated polysaccharides from seaweed are highly active natural substances having valuable applications. In the present paper, attempts have been made to discuss the physicochemical and structural features of polysaccharides isolated from red marine alga Alsidium corallinum (ACPs) and its protective effect in hepatic impairments induced by tebuconazole (TBZ) in rats. Structural features were determined using High performance liquid chromatography, Fourier transformed infrared, and solid state ¹H and ¹³C-Nuclear magnetic resonance analysis. ACPs are found to be hetero-sulfated-anionic polysaccharides that contained carbohydrates, sulfate groups and uronic acids. In vitro biological activities suggested the effective antioxidant and antimicrobial capacities of ACPs. For antioxidant testing in vivo, the biochemical analysis and plasma profiles displayed that oral administration of ACPs could mitigate blood lipid indicators, including total cholesterol, triglyceride, low and high density lipoprotein cholesterol, bilirubin, liver function indexes involving alanine aminotransferase and aspartate aminotransferase, showed that ACPs possessed obvious antioxidant activities. Besides, the intervention of ACPs potentially inhibited lipid peroxidation, protein oxidation, key enzymes of lipid metabolism (<0.001) and increased levels and antioxidant status (<0.05). Histomorphological observation confirmed that ACPs intervention could partially repair liver injuries caused by TBZ. The computational results showed that A. corallinum monosaccharides bound 1JIJ, 1HD2 and 1WL4 receptors with acceptable affinities, which together with deep embedding and molecular interactions support the antioxidant, antimicrobial and hypolipidemic outlined effects in the in vitro and in vivo findings. In view of their prominent antioxidant effects, ACPs stand for promising candidates in liver diseases and need be considered in pharmaceutical applications.

Dyslipidemia is a disorder where abnormally lipid concentrations circulate in the bloodstream. The disorder is common in type 2 diabetics (T2D) and is linked with T2D comorbidities, particularly cardiovascular disease. Dyslipidemia in T2D is typically characterized by elevated plasma triglyceride and low high-density lipoprotein cholesterol (HDL-C) levels. There is a significant gap in the literature regarding dyslipidemia in rural parts of Africa, where lipid profiles may not be routinely captured through standard surveillance activities. This study aimed to characterize the prevalence and demographic profile of dyslipidemia in T2D patients in the rural community of Ganadougou, Mali. We performed a cross-sectional study of 104 subjects with T2D in Ganadougou between November 2021 and March 2022. Demographic and lipid profiles were collected through cross-sectional surveys and blood tests. The overall prevalence of dyslipidemia in T2D patients was 87.5% (91/104), which did not differ by sex (p = .368). High low-density lipoprotein cholesterol (LDL-C) was the most common lipid abnormality (78.9%, [82/104]). Dyslipidemia was associated with age and hypertension status (p = .013 and p = .036, respectively). High total and high LDL-C parameters were significantly associated with hypertension (p = .029 and p = .006, respectively). In low-resource settings such as rural Mali, there is a critical need to improve infrastructure for routine dyslipidemia screening to guide its prevention and intervention approaches. The high rates of dyslipidemia observed in Gandadougou, consistent with concomitant increases in cardiovascular diseases in Africa suggest that lipid profile assessments should be incorporated into routine medical care for T2D patients in African rural settings.

Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statin, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a) and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT’s target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk.

Methylmercury (MeHg) intoxication is a global health concern. Although MeHg neurotoxicity is well-recognized, less is known about MeHg's effects on metabolism. In this study, we evaluated MeHg intoxication (20mg/L in drinking water for 20 days) effects on liver and epididymal white fat (EWF) in young ApoE knockout (ko) and wild-type mice. The former is well-known to show spontaneous dyslipidemia. Hg levels in hair, liver, and EWF were measured to assess the degree of MeHg exposure. We also evaluated body weight gain, plasma triglycerides, total cholesterol levels, and liver injury by assessing steatosis score, AST, ALT, SOD, and TBAR levels. To evaluate EWF, we analyzed mean wet weight and adipocyte diameter, plasma leptin levels and metabolomics. Hg levels were markedly higher among intoxicated mice. ApoE ko mice showed higher Hg in the hair but lower levels in the liver and EWF than wild-type controls. Among wild-type mice, MeHg compromised weight gain and increased liver TBAR levels compared to non-challenged controls. Among non-intoxicated mice, ApoE deficiency significantly increased triglyceride, total cholesterol, and liver transaminases with reduced EWF wet weight, hepatic SOD, and plasma leptin levels. MeHg accumulation together with ApoE deficiency elevated total cholesterol, triglycerides, hepatic transaminases, and TBARS. We found distinct EWF metabolite activity in different scenarios of ApoE deficiency and MeHg intoxication, highlighting increased cardiovascular risk especially when both challenges occur. Further studies are required to elucidate the underlying mechanisms involved in these effects and the target nutritional interventions in most need to ameliorate them.

Alzheimer’s disease (AD) is the most common form of neurodegenerative disease worldwide. A large body of work implicates insulin resistance in the development and progression of AD such that AD may be a form of brain insulin resistance. Moreover, impairment in mitochondrial function, a common symptom of insulin resistance, now represents a fundamental aspect of AD pathobiology. Ceramides are a class of bioactive sphingolipids that have been hypothesized to drive insulin resistance. Here we describe preliminary work that tests the hypothesis that hyperinsulinemia pathologically alters cerebral mitochondrial function in AD mice via accrual of the ceramides. Homozygous male and female ApoE4 mice were given chronic injections of PBS (control), insulin, myriocin (an inhibitor of ceramide biosynthesis), or insulin and myriocin over four weeks. Cerebral ceramide content was assessed using liquid chromatography-mass spectrometry. Mitochondrial oxygen consumption rates were measured with high-resolution respirometry, and H2O2 emissions were quantified via biochemical assays on brain tissue from the cerebral cortex. Significant increases in brain ceramides and impairments in brain oxygen consumption were observed in the insulin-treated group. These hyperinsulinemia-induced impairments in mitochondrial function were reversed with the administration of myriocin. Altogether, these data demonstrate a causative role for insulin in promoting brain ceramide accrual and subsequent mitochondrial impairments that may be involved in AD expression and progression.

Objectives To determine the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA) from animal and plant sources on glucolipid metabolism and lipoprotein subfractions in type 2 diabetic patients with dyslipidemia. Methods Participants were recruited from the diabetes clinic at the Guanlin Hospital, Yixing City in Jiangsu province, China, from March 2017 through June 2017. Ninety participants were randomly assigned to take 3g/day fish oil (FO, containing EPA and DHA), 3g/day perilla oil (PO, containing ALA), or 3g/day blend oil containing fish oil and linseed oil (BO, containing EPA, DHA and ALA) for 3 months. The levels of serum glucose, glycated hemoglobin (HbA1c), C-peptide, triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-HDL, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), lipoprotein a (Lp(a)), and free fatty acids were determined at baseline and after the 3 months. In addition, four fatty acids in serum and red blood cells membranes (RBCm) were analyzed using gas chromatography-mass spectrometry. The Lipoprint System was used to determine the lipoprotein subfractions. Results All 90 participants completed the final 3-month follow-up at the end of the study. After three months of intervention, blood glucose and HbA1c levels in the PO group were significantly lower than those at the baseline (p < 0.05). On the other hand, in the BO group, the HbA1c, non-HDL, Apo A1 and Lp(a) levels were significantly lower, while the C-peptide levels were significantly higher after intervention compared to the baseline (p < 0.05). In the FO group, the HbA1c and TG levels were significantly lower after the intervention compared to the baseline (p < 0.05). In addition, at the end of the study, there was significant increase in the levels of DPA and DHA in serum and RBCm of the FO group (p < 0.05), while in the BO group, there was significant increase in the levels of EPA, DPA and DHA in RBCm (p < 0.05). Finally, the FO group had the highest levels of large HDL subfractions compared to the BO and PO groups, but had the lowest levels of small HDL subfractions among the three groups. Conclusion For patients with diabetes, plant-derived ω-3 PUFAs are more effective at controlling blood glucose than animal-derived ω-3 PUFAs. However, animal-derived ω-3 PUFAs play a critical role in controlling blood lipids. Particularly, fish oil can effectively increase the beneficial large HDL subfractions and reduce the nonbeneficial small HDL subfractions. Both the animal- and plant-derived ω - 3 PUFAs have practical value in improving glucose and lipids metabolism in T2DM patients with dyslipidemia.

Background: The diagnosis of metabolic syndrome (MetS) is a challenge in people with spinal cord injury (SCI). We aimed at identifying clinical risk factors or early markers of MetS in SCI that would facilitate a timely diagnosis and implementation of preventive/therapeutic strategies. Methods: 168 patients with chronic (>1 year) SCI underwent clinical and biochemical evaluations. MetS was diagnosed according to modified criteria of the International Diabetes Federation validated in people with SCI. Results: MetS was diagnosed in 56 of 132 men (42.4%) and 17 of 36 women (47.2%). At univariate regression analyses, putative predictors of MetS were an older age, a higher number of comorbidities, a lower insulin-sensitivity, the presence and intensity of pain, a shorter injury duration, a poorer leisure time physical activity (LTPA) and an incomplete motor injury. At the multiple regression analysis, a significant independent association with MetS only persisted for a poorer LTPA in minutes/week (OR: 0.998, 95%CI: 0.996, 0.999) and more severe pain symptoms as assessed by numeral rating scale (OR: 1.353, 95%CI: 1.085, 1.793). Conclusions: In patients with SCI, intense pain symptoms and poor LTPA may suggest a high likelihood of MetS, regardless of age, SCI duration, motor disability degree, insu-lin-sensitivity and comorbidities.

AIM Non-alcoholic　fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator (SPPARMα), has been reported to ameliorate liver function among patients with dyslipidemia. However, there are not many reports of the clinical effects of the pemafibrate. This study aims to summarize the experience of using pemafibrate and analyze the effects on liver function in patients with dyslipidemia. METHODS One hundred twelve cases of hyperlipidemia receiving pemafibrate 0.2 mg/day were retrospectively enrolled in this study. Age, gender, BMI, complications, concomitant medications, serum parameters (TG, HDL-C, LDL-C, AST, ALT, γGTP, ALP, platelets, M2BPGi, Cre, eGFR, HbA1c, blood glucose level at any time) were investigated and evaluated. RESULTS Pemafibrate administration significantly improved serum TG and HDL-C, but not in LDL-C. Serum AST, ALT, γGTP, and ALP were also significantly improved. The fib-4 index, a liver fibrosis score, did not change significantly, but M2-BPGi, an index of fibrosis, decreased significantly. No correlation was observed between each lipid parameter and ALT, and ALT decreased independently of the lipid parameters. Conclusions As we expected, pemafibrate demonstrated a lipid-improving effect without adversely affecting hepatic and renal functions. An unexpected finding was the decrease in ALT that was independent of lipid parameters.

Area covered: These drugs, particularly calcineurin inhibitors, have very narrow therapeutic windows, i.e., they have numerous drug-related side effects. Herein, we focus on the most frequent immunosuppressive drug-related side effects that we encounter in kidney-transplant recipients: namely nephrotoxicity, post-transplant diabetes mellitus, leukopenia, anemia, dyslipidemia, mouth ulcers, hypertension, and viral reactivations (cytomegalovirus and BK virus). However, other therapies that are used after kidney transplantation, e.g., valcancyclovir, may also contribute to adverse events such as leukopenia. For each side-effect, we suggest how it can be prevented and how to treat it when present.

Fiber-rich green river Aonori alga is mass-cultivated in Japan; it has been reported to reduce inflammation and improve metabolic health in humans. Peroxisome proliferation-activated receptor (PPARs) are associated with metabolic disorders such as obesity and type 2 diabetes (T2DM). We evaluated the effects of supplementation with NBF2, a formula made of algal and junos citrus biomaterials, on metabolic markers in obese and diabetic rats. An experimental study was performed using 18 obese and hyperglycemic Otsuka Long-Evans Tokushima Fatty (OLETF) rats randomly assigned to high dose NBF2 (20mg/kg; n=6), low dose (10mg/kg; n=6) NBF2 drink for 6 weeks, whereas OLETF control rats received similar amount of tap water (vehicle; n=6). LETO rats were used as normal controls (n=8). Biospecimens were taken for ELISA and real-time PCR. Both high dose and low dose NBF2 increased brown adipose tissue (BAT) mass and adiponectin (APN), improved insulin sensitivity, and significantly improved glycemic and lipid (TG, LDL-c) profiles in NBF2-supplemented OLETF rats after a 6-week supplementation with NBF2 (vs. OLETF controls), as well as LDL-c (p<0.05). During the glucose tolerance test (OGTT), both NBF2 groups and LETO rats had normal glycemia by 90-minute time-point (vs. OLETF controls; p<0.01). Furthermore, intake of NBF2 up-regulated PPARa/g-mRNA and Sirt2-mRNA gene expressions in BAT, and improved blood pressure profile in OLETF rats. Findings from this research suggest that intake of NBF2 formula induces dual PPAR-a/g and Sirt2 activation, providing insights on beneficial prophylactic and therapeutic effects of this NB2 formula on dyslipidemia and hyperglycemia in T2DM.

Alcohol abuse can lead to alcoholic liver disease, becoming a major global burden. Hovenia dulcis fruit peduncle polysaccharides (HDPs) has the potential to alleviate alcoholic liver injury may play essential roles in treating for alcohol-exposed liver disease, however, the hepatoprotective effects and mechanisms remain unclear. In this study, the hepatoprotective effects of HDPs and its potential mechanisms were investigated in alcohol-exposed mice by liver metabolomics and gut microbiome. The results found that HDPs reduced medium-dose alcohol-caused dyslipidemia (significantly elevated T-CHO, TG, LDL-C), elevated liver glycogen levels and inhibited intestinal-hepatic inflammation (significantly decreased IL-4, IFN-γ and TNF-α), consequently reversing hepatic pathological changes. By applying gut microbiome analysis, HDPs showed significant decreases in Proteobacteria while significant increases in Firmicutes at the phylum level, and increased Lactobacillus abundance while decreased Enterobacteria abundance, maintaining the composition of gut microbiota. Further hepatic metabolomics analysis revealed that HDPs had a regulatory effect on hepatic fatty acid metabolism, by increasing the major metabolic pathways including arachidonic acid metabolism and glycerophospholipid metabolism and identified two important metabolites C00157 and C04230 involved in the above metabolism. Overall, HDPs reduced intestinal dysbiosis and hepatic fatty acid metabolism disorders in alcohol-exposed mice, suggesting that HDPs has a beneficial effect on alleviating alcohol-induced hepatic metabolic disorders.

Ozonated sunflower oil (OSO) is well known functional oil with its antioxidant, antimi-crobial, anti-allergic, and skin-moisturizing properties. However, studies on the effects of OSO on high-cholesterol diet (HCD)-induced metabolic disorders have been scarce. In the current study, we aimed to determine the anti-inflammatory effects of OSO on lipid me-tabolism in adult hypercholesterolemic zebrafish and its embryo. Microinjection of OSO (final 2%, 10 nL) into zebrafish embryos under presence of carboxymethyllysine (CML, 500 ng) protected acute embryo death upto 61% survival, while sunflower oil (final 2%) showed much less protection around 42% survival. The microinjection of OSO was more effective than SO to inhibit reactive oxygen species (ROS) production and apoptosis in the CML induced embryo toxicity. Intraperitoneal injection of OSO under presence of CML protected acute death from CML-induced neurotoxicity with improved hepatic inflamma-tion, less detection of ROS and interleukin (IL)-6, and lowering blood total cholesterol (TC) and triglyceride (TG), while SO-injected group did not protect the CML-toxicity. Long-term supplementation of OSO (final 20%, wt/wt) with HCD for 6 months resulted higher sur-vivability than HCD alone group or HCD+SO group (final 20%, wt/wt) with significant lowering of plasma TC and TG levels. The HCD+OSO group showed the least hepatic in-flammation, fatty liver change, ROS, and IL-6 production. In conclusion, short-term treat-ment of OSO by injection exhibited potent anti-inflammatory activity against acute neuro-toxicity of CML in zebrafish and its embryo. Long-term supplementation of OSO in diet also revealed the highest survivability and blood lipid-lowering effect through potent an-ti-oxidant and anti-inflammatory activity.

Calpain is delineated as a superfamily of cysteine proteases containing a CysPC motif within their genes. Among the fifteen species of mammalian homologs, calpain-1 and -2, which are categorized as conventional isozymes, execute limited proteolysis in a calcium-dependent fashion. Accordingly, the calpain system participates in physiological and pathological phenomena, encompassing cell migration, apoptosis, skeletal muscle integrity, and synaptic plasticity. The dysregulation of the calpain system has been inextricably linked to a multitude of diseases, such as ischemic and degenerative diseases, rendering it a subject of profound interest in the fields of basic research and pharmaceutical development aimed at therapeutic interventions. Recent investigations have unveiled the contributions of both conventional and unconventional calpains to the pathogenesis of cardiometabolic disorders, such as atherosclerosis, diabetes, and hepatic diseases. Consequently, the present review accentuates the pivotal role of calpains in the complications of cardiometabolic diseases and embarks upon a discourse regarding calpains as molecular 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.

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.

Preeclampsia, a hypertensive disease of pregnancy of unknown etiology, is intensely studied as a model of cardiovascular (CVD) disease not only due to multiple shared pathologic elements, but also because changes that develop over decades in CVD disease appear and resolve within days in preeclampsia. Those affected by preeclampsia and their offspring experience increased lifetime risks of CVD. At the systemic level, preeclampsia is characterized by increased cellular, membrane, and blood levels of cholesterol, however, cholesterol dependent signaling such as canonical Wnt/βcatenin, Hedgehog, and endothelial nitric oxide synthase is downregulated indicating a cholesterol deficit with upregulation of cholesterol synthesis and efflux. Hypoxia related signaling in preeclampsia also appears paradoxical with increased Hypoxia Inducible Factors (HIF) in the placenta but measurably increased oxygen in maternal blood in placental villous spaces. This review addresses the molecular mechanisms by which excessive systemic cholesterol and deficient cholesterol dependent signaling may arise from the effects of dietary lipid variance causing the cellular hypoxia which characterizes preeclampsia.