REVIEW | doi:10.20944/preprints202104.0109.v1
Subject: Biology, Physiology Keywords: Leptin, Animal Communication, Electric Fish, Singing Mice, Metabolism, Energetics
Online: 5 April 2021 (12:11:15 CEST)
Animal communication signals are regulated by multiple hormonal axes that ensure appropriate signal targeting, timing, and information content. The regulatory roles of steroid hormones and many peptide hormones are well understood and documented across a wide range of vertebrate taxa. Two recent studies have reported a novel function for leptin, a peptide hormone central to energy balance regulation: regulating communication signals of weakly electric fish and singing mice. With only limited evidence available at this time, a key question is just how widespread leptinergic regulation of communication signals is within and across taxa. A second important question is what features of communication signals are subject to leptinergic regulation. Here we consider the functional significance of leptinergic regulation of animal communication signals in the context of both direct and indirect signal metabolic costs. Direct costs arise from metabolic investment in signal production, while indirect costs arise from the predation and social conflict consequences of the signal’s information content. We propose a preliminary conceptual framework for predicting which species will exhibit leptinergic regulation of their communication signals and which signal features leptin will regulate. This framework suggests a number of directly testable predictions within and across taxa. Accounting for additional factors such as life history and reproductive strategies will likely require modification or elaboration of this model.
ARTICLE | doi:10.20944/preprints202011.0561.v1
Subject: Medicine & Pharmacology, Allergology Keywords: leptin; cord leptin; pregnancy; intrauterine growth restriction; birth weight
Online: 23 November 2020 (08:39:13 CET)
Introduction: Leptin is a polypeptide hormone and in pregnancy it is secreted by the placenta and maternal and fetal adipose tissues. The expression of leptin and its specific receptors is observed in the uterine endometrium which indicates leptin involvement in the implantation process and embryonic/fetal development. Normal leptin production is a factor responsible for uncomplicated gestation, embryo development and fetal growth. Objective: To compare at delivery maternal serum and cord blood leptin concentrations in normal pregnancies and in pregnancies complicated by intrauterine growth restriction (IUGR). Material and methods: The study was performed in 25 pregnant women with isolated IUGR diagnosed by ultrasonography (study subjects) and in 194 pregnant women without any comorbid health conditions (controls). Leptin concentrations in maternal serum and in cord blood samples collected at delivery were measured by ELISA and subsequently analyzed by maternal Body Mass Index (BMI), mode of delivery, and infant gender and birth weight. For comparative analyses of normally distributed variables, parametric tests were used, i.e. the Student-t to test the assumption of homogeneity or non-homogeneity of variance and a One-Way ANOVA when more than two groups were compared. The non-parametric Mann-Whitney test was used when the distribution was not normal. The Pearson correlation coefficient was calculated to assess the correlation between normally distributed variables (p<0.05). Results: In pregnancies complicated by IUGR, the mean maternal serum leptin concentration at delivery was significantly higher (52.73 ± 30.49 ng/mL) than in normal pregnancies (37.17 ± 28.07 ng/mL) (p=0.01). The mean cord blood leptin concentration in pregnancies complicated by IUGR was 7.97 ± 4.46 ng/mL and significantly lower than in normal pregnancies (14.78 ± 15.97 ng/mL) (p=0.04). In normal pregnancies, but not in pregnancies complicated by IUGR, a statistically significant correlation was established between maternal serum leptin concentrations and maternal BMI at delivery (r=0,22; p=0.00). No statistically significant correlation was found between cord blood leptin concentrations and maternal BMI in either study subjects or controls. In normal pregnancies, but not in pregnancies complicated by IUGR, a strong correlation was observed between cord blood leptin concentrations and birth weight (r=0,23; p=0.00). In both study subjects and controls, there were no correlations between leptin concentrations in maternal serum and cord blood and infant gender and mode of delivery. Conclusions: Elevated maternal blood leptin concentrations in pregnancies complicated by IUGR may indicate a significant adverse effect of elevated leptin on fetal growth. Enhanced leptin production by the placenta suggests leptin as a candidate marker of placental insufficiency. The differences in leptin concentrations, measured in maternal serum and in cord blood, between the study subjects and controls suggest that deregulated leptin levels may increase the risk of obstetric complications associated with placental insufficiency.
ARTICLE | doi:10.20944/preprints202202.0066.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: serum leptin; proximal gastric cancer
Online: 4 February 2022 (07:31:59 CET)
Background: The aim of the present study was to determine the correlation between obesity, serum levels of leptin and proximal gastric cancer. Methods: Sixty-four gastric cancer patients operated on with curative intent were included in the study. We determined the correlation between the preoperative serum levels of leptin and the tumor`s location. Results: Serum leptin levels were correlated significantly with the proximal third location (p = 0.04), gastric outlet obstructing tumors (p < 0.0001), CRP levels (p = 0.03) and BMI (p < 0.0001). Patients with high serum levels of leptin had significantly more intestinal types of gastric cancer (p = 0.033) and better differentiation compared to patients with low serum leptin levels (p = 0.009). The linear regression model determined the proximal tumor location (beta: 0.467; p = 0.045), BMI (beta: 0.657; p = 0.001), high preoperative serum albumin (beta: 0.563; p = 0.016) and the presence of pyloric stenosis (beta: 0.525; p = 0.006) as related significantly to serum leptin levels. The Cox proportional hazard model identified age (HR: 0.003; 95%CI: 0-0.794; p = 0.041), preoperative serum levels of leptin (HR: 0.125; 95%CI: 0.018-0.887; p = 0.037) and the number of extracted LNs (HR: 0.001; 95%CI: 0-0.677; p = 0.038) as independent prognostic factors. Conclusions: Serum levels of leptin were significantly elevated in patients with proximal gastric cancer, suggesting that the leptin`s effect might be due to its systemic secretion. This might explain the higher incidence of proximal gastric cancer in obese patients. Elevated serum leptin levels were an independent prognostic factor.
ARTICLE | doi:10.20944/preprints202109.0263.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: serum leptin; nutritional status; laparoscopic gastrectomy
Online: 15 September 2021 (14:15:06 CEST)
Background: Laparoscopic surgery produces lesser postoperative inflammation with a smaller cytokine and leptin response, and might thus reduce postoperative anorexia compared to open surgery. The aim of the present study was to determine the role of serum leptin in postoperative anorexia after laparoscopic gastric cancer surgery. Methods: Fifty-four consecutive patients with adenocarcinoma of the stomach were operated on either with open or laparoscopic surgery. Correlations were determined between the serum levels of leptin, clinico-pathological characteristics, serum haemoglobin and albumin. Results: Serum leptin levels on day seven were correlated significantly to gender (p=0.004), BMI (p=0.002) and tumour grade (p=0.033). In the patients with CRP < 100 mg/l the leptin levels on day seven were significantly lower after the laparoscopic operation (p=0.042) and in patients with lower BMI (p=0.001). The linear regression model determined a significant correlation between the relative concentration of leptin on day seven and laparoscopic surgery (Beta -0.688; p < 0.0001), gender, BMI, location of the tumour, T stage, N stage, perioperative therapy, tumour grade, perineural invasion, Lauren histological type and ulceration. In patients with CRP levels below 100 mg/ml the serum level of albumin on day seven after surgery was significantly higher in patients after laparoscopic surgery. Conclusion: Laparoscopic surgery produced significantly lower relative leptin concentrations on day seven, and higher serum albumin levels in the subgroup with CRP levels below 100 mg/l at discharge. These results suggested that laparoscopic gastric cancer surgery might reduce postoperative leptin response, leading to a better nutritional status at discharge compared to open surgery.
Subject: Medicine & Pharmacology, Nutrition Keywords: HMW adiponectin; leptin; dietary patterns; breast cancer survivors
Online: 20 August 2021 (15:30:06 CEST)
Dietary pattern (DP) and its relationship with disease biomarkers has received recognition in nutritional epidemiology investigations. However, DP relationships with adipokines (i.e., adiponectin and leptin) among breast cancer survivors remain unclear. Therefore, we assessed relationships between DP with high molecular weight (HMW) adiponectin and leptin concentration among breast cancer survivors. This cross-sectional study involved 128 breast cancer survivors who attended the oncology outpatient clinic at two main government hospitals in East Coast of Peninsular Malaysia. The serum concentration of HMW adiponectin and leptin were measured using enzyme-linked immunosorbent assay (ELISA) kits. Reduced rank regression method was used to analyze DP. Relationships between DP with HMW adiponectin and leptin were examined using regression models. Findings showed that a one-unit increase in the ‘energy-dense, high-saturated fat and low-fiber’ DP z-score was associated with a 0.41 µg/mL lower HMW adiponectin (95% CI: -0.806, -0.014) which was independent of age, BMI, cancer stage, duration since diagnosis, education level and occupation status. A similar relationship with leptin concentration was not observed. In conclusion, ‘energy-dense, high-saturated fat and low-fiber’ DP, which is characterized by high sugar-sweetened drink and fat-based spread but low intake of fruits and vegetables, is an unhealthy dietary pattern and unfavorable for HMW adiponectin concentration but not for leptin. These findings could serve as a basis in developing specific preventive strategies that are tailored to the growing population of breast cancer survivors.
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Roux-en-Y gastric bypass surgery; Weight loss; Food intake; Oral glucose tolerance; Leptin; Leptin receptors; Zucker Fatty fa/fa rats
Online: 12 February 2021 (13:11:41 CET)
Leptin is the archetypal adipokine that promotes a negative whole-body energy balance largely through its action on brain leptin receptors. As such, the sustained weight loss and food intake suppression induced by Roux-en-Y gastric bypass (RYGB) surgery have been attributed to enhancement of leptin receptor signalling. We formally revisited this idea in Zucker Fatty fa/fa rats, an established genetic model of leptin receptor deficiency, and carefully compared their body weight, food intake and oral glucose tolerance after RYGB with that of sham-operated fa/fa (obese) and sham-operated fa/+ (lean) rats. We found that RYGB rats sustainably lost body weight, which converged with that of lean rats and was 25.5 % lower than that of obese rats by the end of the 4 week study period. Correspondingly, daily food intake of RYGB rats was similar to that of lean rats from the second postoperative week, while it was always at least 33.9 % lower than that of obese rats. Further, oral glucose tolerance of RYGB rats was normalized at the forth postoperative week. These findings assert that leptin is not an essential mediator of the sustained weight loss and food intake suppression as well as the improved glycemic control induced by RYGB, and instead point to additional circulating and/or neural factors.
ARTICLE | doi:10.20944/preprints202006.0274.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: adolescent idiopathic scoliosis; bone turnover markers; leptin; body composition
Online: 21 June 2020 (14:33:41 CEST)
The link between scoliotic deformity and bone metabolism in adolescent idiopathic scoliosis (AIS) has not been well researched. Moreover, the data concerning the cross-talk between fat tissue content/hormonal activity and bone markers in this group of patients are lacking. The objective of this study was to correlate the extent of scoliotic-curve severity with the bone turnover vs. leptin level and nutritional status in girls with AIS. The study encompassed 77 AIS girls, aged 14.7 ± 2.17 years. Scoliotic curve severity assessed by Cobb’s angle was categorized as mild (10-19o) moderate (20-39º) or severe (≥40º). Corrected height, weight, waist and hip circumferences were measured and body mass index (BMI), corrected height Z-score, BMI Z-score and waist/height ratio (WHtR) were calculated for the entire group. Body composition parameters: fat mass (FAT), fat-free mass (FFM) and predicted muscle mass (PMM) were determined using a bioelectrical impedance analyzer. Bone turnover markers (osteocalcin (OC) and amino terminal of collagen cross-links NTx) and leptin levels were assessed in serum. Multiple regression analysis showed that, OC, NTx (negatively with p<0.05) and leptin (positively with p<0.01) were significantly associated with curve severity in AIS girls. Moreover, Cobb’s angle was positively correlated with W/HtR (p<0.01)and FAT (p<0.05). One-way analysis of variance (ANOVA) revealed significant differences in leptin (p<0.05 vs. mild only), OC (p<0.05 vs. mild and moderate)) and W/HtR (p<0.01 and p<0.05 vs. mild and moderate respectively) between the three AIS severity subgroups. OC was significantly lower in the severe AIS subgroup, while leptin and W/HtR were significantly higher. Significant correlations between leptin and anthropometrical parameters as BMI z-score and W/HtR were shown. Leptin level correlated also significantly with BMI z score (p<0.001), W/HtR (p<0.0001) and body composition parameters (p<0.000001). Moreover, there was a significant negative correlation between NTx and leptin level (p<0.05). Bone metabolism in AIS girls seems to be altered and significantly related to the scoliotic curve severity. Leptin may be a crucial link in the cross-talk between bone turnover and body composition in this group of patients. Further studies concerning this topic are needed.
ARTICLE | doi:10.20944/preprints202108.0019.v1
Subject: Medicine & Pharmacology, Allergology Keywords: leptin; JAK/STAT pathway; myocardial infarction; hemodynamics; arrhythmias; dyslipidaemia; inflammation; cardiac remodeling
Online: 2 August 2021 (11:24:57 CEST)
Hyperleptinemia potentiates the effects of many atherogenic factors, such as inflammation, platelet aggregation, migration, hypertrophy, proliferation of vascular smooth muscle cells, and endothelial cell dysfunction. The present study analysed the eﬀects of long-term hyperleptinemia in an in vivo myocardial ischemia-reperfusion model to demonstrate whether the in vivo deleterious effect also affects cardiac structure and function. Rats by were subcutaneously administered leptin for 8 days to estimate the involvement of the JAK/STAT pathway. Data from 58 male Wistar rats were included in the final analysis. Myocardial infarction (MI) was modelled by the 30-minute ligation of the main left coronary artery followed by 120-minute reperfusion. Hemodynamic measurements, electrocardiography monitoring, echocardiography, myocardial infarct size and area at risk, blood biochemical parameters, leptin, IL-6, TNF-alpha, FGF-21, and cardiomyocyte morphology were measured. Statistical analyses were performed using IBM SPSS Statistics v.26. Seven-day hyperleptinemia in rats led to increased an blood pressure and heart rate, myocardial hypertrophy, impaired LV function, an increased frequency of ischemic arrhythmias, dyslipidaemia, systemic inflammation, and an increased size of induced myocardial infarction. The blockade of the JAK/STAT signalling pathway effectively reversed the negative effects of leptin, including increased blood pressure and total cholesterol.
ARTICLE | doi:10.20944/preprints202104.0041.v1
Subject: Life Sciences, Biochemistry Keywords: Leptin; Metabolism; Amyotrophic Lateral Sclerosis (ALS); TAR DNA binding protein (TDP-43).
Online: 2 April 2021 (11:09:21 CEST)
Amyotrophic Lateral Sclerosis (ALS) is an irreversible neurodegenerative disease with no known cure. Recent studies suggest a strong metabolic component in ALS pathogenesis and have shown an inverse relationship between leptin levels and ALS progression, although the effects of leptin as a treatment have not yet been studied. Therefore, we aim to examine whether the acute treatment with leptin has beneficial effects on brain pathology and cognitive function in the transgenic TDP43A315T line of ALS. Mice were treated intranasally (IN) with 0.03mg/kg of leptin or vehicle (VH) daily for 7 days. Data showed a progressive decline in body weight and motor coordination in TDP43A315T mice. Moreover, Lep-treated TDP43A315T mice showed an earlier disease onset, along with an improvement in motor performance. Altered levels of some of the adipokines and metabolic proteins studied were found in TDP43A315T mice, which were differently expressed among Lep-treated and VH-treated animals. Furthermore, some correlations were found among the serum levels of this proteins in WT and TDP43A315T mice. As far as we know, this is the first pilot study to provide evidence of the therapeutic effect of leptin treatment in a mice model of ALS, although further studies are needed to expound on the underlying mechanisms.
REVIEW | doi:10.20944/preprints201905.0040.v1
Subject: Life Sciences, Other Keywords: breast cancer; sleep; IL-6; hypocretin/orexin; leptin; EEG; autonomic nervous system
Online: 6 May 2019 (08:52:31 CEST)
Sleep is essential for health. Indeed, poor sleep is consistently linked to the development of systemic disease, including depression, metabolic syndrome, and cognitive impairments. Further evidence has accumulated suggesting a role for sleep in cancer initiation and progression (primarily breast cancer). Indeed, patients with cancer and cancer survivors frequently experience poor sleep, manifested as insomnia, circadian misalignment, hypersomnia, somnolence syndrome, hot flushes, and nightmares. These problems are associated with a reduction in patients’ quality of life and increased mortality. Due to the heterogeneity among cancers, treatment regimens, patient populations, and lifestyle factors, the etiology of cancer-induced sleep disruption is largely unknown. Here, we discuss recent advances in understanding the pathways linking cancer and the brain and how this leads to altered sleep patterns. We describe a conceptual framework where tumors disrupt normal homeostatic processes, resulting in aberrant changes in physiology and behavior that are detrimental to health. Finally, we discuss how this knowledge can be leveraged to develop novel therapeutic approaches for cancer-associated sleep disruption, with special emphasis on host-tumor interactions.
ARTICLE | doi:10.20944/preprints202301.0191.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: BDNF; CRP; C-peptide; leptin; pregnancy; skinfold thickness; thyroid hormones; type-1 diabetes mellitus
Online: 11 January 2023 (02:57:33 CET)
The study aimed to determine the relationship between glucose, C-peptide, BDNF, and leptin between mother and fetus and neonatal weight. Methods: In the prospective observational cohort study, we included 66 women with T1DM. According to the z-score for neonatal weight, patients were divided into Healthy weight neonates (n=42) and Overweight neonates (n=24). The maternal blood samples were taken during pregnancy and cesarean section when the umbilical vein blood sample was also withdrawn. The maternal vein sera were analyzed for fasting glucose, CRP, leptin, BDNF, TSH, FT3, and FT4. The umbilical vein sera were analyzed for glucose, C-peptide, leptin, TSH, FT3, FT4, and BDNF concentration. The neonatologist measured the skinfold thickness on the third day of neonatal life. Results: A strong correlation was confirmed between maternal and umbilical vein glucose concentration and maternal glucose and C-peptide in umbilical vein blood. A negative correlation was found between the concentration of BDNF in the umbilical vein and glucose in maternal blood. A strong correlation was seen between BMI and maternal blood leptin concentration, neonatal fat body mass, and umbilical vein blood leptin concentration. Increased odds for Overweight neonates were BMI, BDNF, and TSH in the first trimester of pregnancy. Maternal leptin concentration decreased the odds of Overweight neonates. Conclusions: Maternal glucose concentrations affect the fetus’s glucose, C-peptide, and BDNF concentrations. Leptin levels increase in maternal blood due to increased body mass index, and in the neonate, its fat body mass is responsible for increased leptin concentrations.
REVIEW | doi:10.20944/preprints201911.0013.v1
Subject: Medicine & Pharmacology, Other Keywords: lung transplantation; body mass index; nutrition; body composition; lean body mass; muscle mass; leptin; sarcopenia; creatinine-height index
Online: 1 November 2019 (13:02:51 CET)
Lung transplantation offers patients with end stage lung disease an opportunity for a better quality of life, but with limited organ availability it is paramount that selected patients have the best opportunity for successful outcomes. Nutrition plays a central role in post-surgical outcomes and historically, body mass index (BMI) has been used as the de facto method of assessing a lung transplant candidate’s nutritional status. Here we review the historical origins of BMI in lung transplantation, summarize the current BMI literature, and review studies of alternative/complementary body composition assessment tools, including lean psoas area, creatinine-height index, leptin, and dual x-ray absorptometry. These body composition measures quantify lean body mass versus fat mass and may provide a more comprehensive analysis of a patient’s nutritional state than BMI alone.