Circulating Leptin Concentrations Research Articles

Neurodevelopmental Programming of Adiposity: Contributions to Obesity Risk.

This review analyzes the published evidence regarding maternal factors that influence the developmental programming of long-term adiposity in humans and animals via the central nervous system (CNS). We describe the physiological outcomes of perinatal underfeeding and overfeeding and explore potential mechanisms that may mediate the impact of such exposures on the development of feeding circuits within the CNS-including the influences of metabolic hormones and epigenetic changes. The perinatal environment, reflective of maternal nutritional status, contributes to the programming of offspring adiposity. The in utero and early postnatal periods represent critically sensitive developmental windows during which the hormonal and metabolic milieu affects the maturation of the hypothalamus. Maternal hyperglycemia is associated with increased transfer of glucose to the fetus driving fetal hyperinsulinemia. Elevated fetal insulin causes increased adiposity and consequently higher fetal circulating leptin concentration. Mechanistic studies in animal models indicate important roles of leptin and insulin in central and peripheral programming of adiposity, and suggest that optimal concentrations of these hormones are critical during early life. Additionally, the environmental milieu during development may be conveyed to progeny through epigenetic marks and these can potentially be vertically transmitted to subsequent generations. Thus, nutritional and metabolic/endocrine signals during perinatal development can have lifelong (and possibly multigenerational) impacts on offspring body weight regulation.

Hyperleptinemia contributes to antipsychotic drug-associated obesity and metabolic disorders.

Despite their high degree of effectiveness in the management of psychiatric conditions, exposure to antipsychotic drugs, including olanzapine and risperidone, is frequently associated with substantial weight gain and the development of diabetes. Even before weight gain, a rapid rise in circulating leptin concentrations can be observed in most patients taking antipsychotic drugs. To date, the contribution of this hyperleptinemia to weight gain and metabolic deterioration has not been defined. Here, with an established mouse model that recapitulates antipsychotic drug-induced obesity and insulin resistance, we not only confirm that hyperleptinemia occurs before weight gain but also demonstrate that hyperleptinemia contributes directly to the development of obesity and associated metabolic disorders. By suppressing the rise in leptin through the use of a monoclonal leptin-neutralizing antibody, we effectively prevented weight gain, restored glucose tolerance, and preserved adipose tissue and liver function in antipsychotic drug-treated mice. Mechanistically, suppressing excess leptin resolved local tissue and systemic inflammation typically associated with antipsychotic drug treatment. We conclude that hyperleptinemia is a key contributor to antipsychotic drug-associated weight gain and metabolic deterioration. Leptin suppression may be an effective approach to reducing the undesirable side effects of antipsychotic drugs.

29 The Role of Leptin and Its Regulation in the Hypothalamus of Neonatal Calves

Abstract The constant occurrence of increased feed intake in offspring exposed to intrauterine growth restriction has been noted across multiple species including ruminants. In ruminants, reduced circulating leptin concentrations from birth through the first week or two of life may influence the development of the appetite center of the hypothalamus. It should able be noted that increased circulating cortisol at birth has been associated with this decreased circulating leptin in the perinatal ruminants, yet information is limited as to any cause and effect relationship between the two hormones. The objectives of these studies were to test directly the effects of exogenous cortisol on leptin concentrations relative to development of the hypothalamus in perinatal calves and voluntary feed intake as yearling. In two experiments, Holstein bulls (n = 27) and calves (n = 32 males; n = 30 females) from commercial Angus cows were assigned to treatments at parturition (day 0). Calves were intravenously infused with either a low cortisol [LC; n = 9, 3.5 ug/kg of body weight (BW)], high cortisol (HC; n = 9, 7.0 ug/kg BW), or a control (CON; n = 9, saline). Calves were administered a half dose of their respective treatment 24h postpartum. Jugular vein blood samples were collected before infusion and daily until d 17 or necropsy. At 5 days of age Holstein bull calves were euthanized where cerebral-spinal fluid (CSF) and hypothalamic tissue were collected. Serum and CSF leptin concentrations were analyzed via RIA. Neuronal growth factors were analyzed in hypothalamus samples via qRT-PCR. In experiment 2, yearling calves entered a GROWSAFE System and daily feed intake (FI) measured. Animals were allowed a two-week adjustment period to a growing ration for heifers and a finishing ration for steers. Heifer body condition scores (BCS) were collected at the beginning and end of the trial. Heifers underwent the feeding trial for 70 days and steers until they obtained a back fat (BF) thickness of 1.15 cm. Blood samples were analyzed similar to experiment 1. All data were analyzed via repeated measures using appropriate models of SAS (SAS Institute Inc., Cary, NC). Perinatal dairy bull calves had decreased (P < 0.013) serum and CSF leptin concentrations of HC and LC calves compared with CON. Hypothalamic expression of BDNF, FGF1 and FGF2 were decreased (P < 0.006) in HC and LC compared with CON. During the feeding trial: BW gain, BCS change, and number of feed events were increased (P = 0.001) in LC compared with HC and CON heifers. However, LC observed greater daily FI (P = 0.047) and tended to have greater final BW (P = 0.080) compared with HC and CON steers. In summary, these data support that exogenous cortisol administered to perinatal calves affects leptin production and the appetite center of the hypothalamus when administered during the neonatal period.

The effect of leptin on trained innate immunity and on systemic inflammation in subjects with obesity.

Leptin is associated with cardiometabolic complications of obesity, such as metabolic syndrome and atherosclerosis. In obese men, the presence of metabolic syndrome is associated with higher circulating leptin and interleukin (IL)-6 concentrations and increased monocyte cytokine production capacity. Here, we investigated the effects of leptin on monocyte function and systemic inflammatory markers in obese individuals. We specifically explored whether leptin can induce long-term changes in innate immune function by inducing innate immune memory (also called trained immunity). We exposed human primary monocytes for 24 h to relevant leptin concentrations in vitro and measured cytokine production. In addition, after removing leptin, we incubated monocytes for 5 d in culture medium, and we restimulated them on day 6 to assess cytokine production capacity, phagocytosis, and foam cell formation. Direct stimulation with leptin did not induce cytokine production, but exposure to 50 ng/mL leptin augmented lipopolysaccharide- and R848-induced tumor necrosis factor α (TNF-α) production after 1 wk. In a separate in vivo study in a cohort of 302 obese subjects (body mass index [BMI] >27 kg/m2, 55 to 81 yr), we measured circulating leptin, inflammatory markers, and cytokine production upon ex vivo stimulation of isolated peripheral blood mononuclear cells. Circulating leptin concentrations positively correlated with circulating IL-1β and IL-6, which was more pronounced in men than in women. Four single nucleotide polymorphisms in the leptin gene influenced circulating IL-6 concentrations in men, suggesting a direct effect of leptin on IL-6. In conclusion, in vitro, leptin does not directly stimulate monocytes to produce cytokines, yet induces long-term monocyte hyperresponsiveness, i.e. trained immunity. In obese subjects, leptin is associated with circulating IL-6 in a sex-dependent manner. The underlying mechanisms of the sex-specific effect of leptin on innate immune cells remain to be further investigated.

Association of serum leptin and resistin levels among obese Saudi patients with acute myocardial infarction in Asir region.

In the current scenario, the importance of cardiac biomarkers in diagnosing, assessing, and managing people with cardiovasculardiscomfort is required. This cross-sectional study examined the relationship between serum leptin and resistin levels among obese people with acute myocardial infarction (AMI) with varying body mass index (BMI). The cardio and diabetic biomarkers among the 77 Saudi patients with hypoxia who lived in the Asir region were analyzed in the study. The patients were categorized into three groups, namely, group 1 (control), group 2 (AMI with normal BMI), and group 3 (AMI with varying BMI). Our results showed a positive correlation between serum glucose, HbA1C, triglycerides, Troponin-I (cTnI), creatine kinase MB (CK-MB), leptin, and resistin in patients with AMI. We also observed significantly lower HbA1C, cholesterol, and insulin values in groups 2 and 3. A statistical difference between the groups with and without AMI and between the genders was noticed. BMI with leptin showed a positive connection in group 3 but no association was observed for groups 1 and 2. A stronger relationship between BMI and leptin levels in men in Group 3 than in women was observed. In all three groups, resistin levels did not correlate with BMI. Thus, circulating leptin concentrations do not significant impact AMI compared to participants with and without AMI. However, resistin levels were considerably higher in obese individuals with AMI. Therefore, we suggest that resistin can be used as a pro-inflammatory marker to detect AMI disorder with varying BMI and as a prognostic marker associated with AMI.

Leptin Resistance Does Not Facilitate Migratory Fattening in Ruby-Throated Hummingbirds (Archilochus Colubris).

In mammals, leptin is an important energy homeostasis hormone produced by adipose tissue. Circulating leptin concentrations correlate positively with fat mass and act in a negative feedback fashion to inhibit food intake and increase energy expenditure, thereby preventing fat gain. For some species, leptin resistance is advantageous during times of year where fat gain is necessary (e.g., prior to hibernation). While the function of leptin in birds remains controversial, seasonal leptin resistance may similarly benefit migratory species. Here, we used the ruby-throated hummingbird (Archilochus colubris) to test the hypothesis that leptin resistance promotes fattening prior to migration. We predicted that during the migratory fattening period, leptin levels should correlate positively with fat mass but should not inhibit food intake or increase energy expenditure, resulting in fattening. We tracked the body (fat) mass, the concentration of leptin-like protein in the urine, and the food intake of 12 captive hummingbirds from August 2021 to January 2022. In a subset of hummingbirds, we also quantified voluntary physical activity as a proxy for energy expenditure. We found remarkable age-related variation in fattening strategies, with juveniles doubling their body fat by mid-September and adults exhibiting only a 50% increase. Changes in fat mass were strongly associated with increased food intake and reduced voluntary activity. However, we found no correlation between leptin-like protein concentration and fat mass, food intake, or voluntary activity. Since increased torpor use has been shown to accelerate migratory fattening in ruby-throated hummingbirds, we also hypothesized that leptin is a mediator of torpor use. In an experimental manipulation of circulating leptin, however, we found no change in torpor use, body fat, or food intake. Overall, our findings suggest that leptin may not act as an adipostat in hummingbirds, nor does leptin resistance regulate how hummingbirds fatten prior to migration.

Comparison of Levels of Telomerase, Oxidative Stress, Adiponectin, Leptin, and Interleukin-6 in First Degree Relatives of Diabetics, Prediabetics, and Diabetics: A Cross-sectional Study

Introduction: Rapid beta-cell senescence caused by telomere shortening is associated with type 2 diabetes. Hence, studying telomere dynamics in prediabetic stages or First Degree Relatives of Diabetics (FDRD) is crucial. Telomere attrition is influenced by oxidative stress, which is prevalent in diabetics, prediabetics, and FDRD due to dyslipidaemia. The relationship between telomerase activity and glycaemic control, insulin resistance, oxidative stress, dyslipidaemia, adipocytokines, and inflammatory markers remains unclear and requires further investigation. Aim: To assess and compare telomerase levels, oxidative stress (malondialdehyde), adipocytokines (leptin, adiponectin, and Interleukin-6 (IL-6), lipid profiles, and Body Fat Percentage (BF%) across the glycaemic spectrum in the Indian population. Materials and Methods: This cross-sectional study was conducted at the Department of Physiology, JIPMER, Puducherry, from 2016 to 2018, involving four groups: Group I (control group, non diabetic, healthy, non FDRD, n=63), Group II (FDRD, non diabetic, n=63), Group III (prediabetics, n=63), and Group IV (diabetics, n=63). Participants aged 30-50 years, matched for age and gender, were recruited. Anthropometric variables, cardiovascular parameters, telomerase levels, Malondialdehyde (MDA), adiponectin, leptin, IL-6, and lipid profiles were assessed. Mean differences were analysed using one-way Analysis of Variance (ANOVA) or Kruskal-Wallis test, while Pearson’s correlation analysis was performed to assess the correlation between telomerase levels, glucose concentration, and BF%. Results: An increasing trend in circulating telomerase levels, lipid profiles, and BF% was observed across the glycaemic spectrum. Circulating leptin concentrations did not differ between the groups. However, there was a decrease in circulating adiponectin concentration as the glycaemic status progressed. Increased MDA levels were observed only in the diabetics group. Telomerase levels showed a significant association with circulating glucose concentration (fasting and postprandial) and BF%. Conclusion: The circulating telomerase level increased along the glycaemic spectrum (non FDRD<FDRD<Prediabetics< Diabetics). The major finding was that telomerase level increases even in normoglycaemic FDRD. Oxidative and inflammatory parameters did not significantly differ in FDRD compared to non FDRD individuals. Notably, adiponectin, Tumour Necrosis Factor (TNF)-α, Low-Density Lipoprotein (LDL), and HighDensity Lipoprotein (HDL) were the parameters that showed changes in FDRD.

Association of genetic variants in Leptin, leptin receptor and adiponectin with hypertension risk and circulating Leptin/Adiponectin changes

BackgroundsHypertension is inheritable, and some candidate genes such as leptin and adiponectin have drawn special concerns. ObjectivesWe performed a meta-analysis on the association of 7 genetic variants in genes encoding leptin, leptin receptor and adiponectin with hypertension risk and circulating leptin/adiponectin changes. MethodsLiterature search, report selection and data extraction were performed by two authors independently. Effect sizes are expressed as odds ratio (OR) or standard mean difference (SMD) with 95% confidence interval (CI). ResultsTotal 32 reports (7432 cases with hypertension and 9218 controls) were meta-analyzed. Overall analyses indicated that rs7799039 (dominant model: OR = 1.67; 95 % CI: 1.03 to 2.71; P = 0.038) and (TTTC)n (allelic model: OR = 1.53; 95 % CI: 1.05 to 2.23; P = 0.028) were significantly associated with hypertension risk. Subgroup analyses indicated that hypertension type, race, diabetes, genotyping method and quality score might be potential causes for between-study heterogeneity. Besides rs2241766, no evidence of publication bias existed for the other variants. Carriers of rs7799039-AG genotype had significantly higher leptin concentrations than carriers of rs7799039-GG genotype (SMD = 1.98; 95 % CI: 0.07 to 3.89; P = 0.042). In Mendelian randomization analyses, an increment of leptin concentrations by 1 ng/mL was causally associated with a 25 % significantly increased risk of hypertension (95 % CI: 1.02 to 10+; P < 0.05). ConclusionsOur findings indicated that leptin gene rs7799039 and (TTTC)n were potential hypertension-candidacy loci, and importantly high circulating leptin concentrations causally precipitated the development of hypertension.

Abstract P078: Excess Risk Of Hypertension Among Black Adults And The Mediating Effects Of Leptin: The Reasons For Geographic And Racial Differences In Stroke (REGARDS) Cohort Study

Background: Leptin is a hypertension-related adipokine. We previously found leptin to associate with greater risk of incident hypertension in non-obese adults. Relative to White adults, Black adults have higher circulating leptin concentration. As such, leptin may be a mediator of the excess burden of incident hypertension among Black adults. Methods: REGARDS recruited 30,239 Black or White adults aged ≥45 years from 48 US states. Leptin was measured from baseline samples among 4,400 participants who attended 2 visits 9 years apart. Modified Poisson regression estimated the relative risk (RR) of incident hypertension (≥140/90 mmHg or use of antihypertensives) of Black relative to White adults, adjusting for risk factors. Inverse odds ratio weighting estimated the % mediation by leptin of the excess hypertension RR among Black relative to White participants in 1,000 bootstrapped samples. Results: In 1,834 participants without prevalent hypertension (mean age 62, 56% women, 25% Black adults), incident hypertension developed in 47% of Black &amp; 32% of White participants. The Table presents the RR for incident hypertension among Black relative to White adults. In the crude model, Black adults had a 52% greater risk of incident hypertension and leptin mediated 20% of this disparity. Similar associations were seen when adjusting for demographics, behaviors, and diseases. After adjusting for measures of adiposity, leptin no longer mediated the disparity. Conclusions: Leptin mediated approximately 20% of the Black-White disparity in hypertension incidence in crude and some adjusted models. These data support that this mediation acts through adiposity.

Seasonal change of circulating leptin associated with testicular activities of the wild ground squirrels (Citellus dauricus).

The purpose of this study was to explore the variations in the circulating leptin concentrations of the wild ground squirrels in relation to seasonal changes in testicular activities. Hematoxylin-eosin staining showed all types of elongated spermatids and spermatogenic cells existed in the testis in April, while the primary spermatocytes and spermatogonia were most advanced stages of germ cells in June. In addition, the primary spermatocytes, secondary spermatocytes, and spermatogonia were most advanced stages of germ cells in September. The highest circulating leptin concentration was consistent with the maximum body weight results from accumulation of adipose tissue in September. The mRNA expression level of leptin receptor (Ob-R) and STAT3 was lowest in June, raised in September, and remained increased in April. Ob-R and STAT3 were stronger staining in the Leydig cells in July. Moreover, the concentrations of testosterone (T) showed the maximum values in April, the minimum values in June, and significant increases in September. Furthermore, it is worth noting that the levels of T increased with the mRNA levels of Ob-R, STAT3, StAR, and testicular steroidogenic enzymes (3β-HSD, P450c17, and P450scc). Moreover, RNA-seq analyses of testis during the different periods showed that a total of 4209 genes were differentially expressed genes (DEGs); further analysis revealed that DEGs related with the Jak/STAT pathways and reproduction were altered. Taken together, the results suggested that the leptin regulated testicular function through the Jak/STAT pathways and testicular steroidogenic factor expressions.

Changes in adiponectin:leptin ratio among older adults with obesity following a 12-month exercise and diet intervention

BackgroundExcess adiposity is characterized by alterations in adipokine secretion such that circulating leptin concentrations are increased with reductions in adiponectin. An emerging biomarker for the assessment of this adipose tissue (AT) dysfunction is the adiponectin:leptin (AL) ratio. A low AL ratio may be suggestive of dysfunctional AT and, consequently, a heightened cardiometabolic disease risk. This ancillary study investigated the relationship between the AL ratio and cardiometabolic health among community-dwelling older adults with obesity, as well as the effects of a 12-month exercise and diet intervention on changes in the AL ratio.MethodsParticipants (n = 163, 70.2 ± 4.7 years, 38.0% male) were randomized to the exercise only group, exercise + nutrient-dense weight maintenance group (exercise + weight maintenance), or exercise + nutrient-dense caloric restriction of 500 kcal/d group (exercise + intentional weight loss) (clinicaltrials.gov #NCT00955903). Total and regional adiposity as determined by magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry (DXA), anthropometrics, and cardiometabolic biomarkers were assessed at baseline and 12 months.ResultsThe AL ratio was significantly (p < 0.05) inversely correlated with body mass index, waist circumference, measures of adiposity, and insulin among all participants at baseline. Among females only, significant positive and inverse correlations were also observed between this ratio and high-density lipoprotein cholesterol and the inflammatory biomarkers high sensitivity C-reactive protein and interleukin-6, respectively. While controlling for biological sex, a significant time by intervention group interaction effect (p < 0.05) was observed such that the AL ratio significantly increased from baseline to study completion among participants in the exercise + weight maintenance group and exercise + intentional weight loss group. Post hoc analysis revealed that the exercise + intentional weight loss group exhibited a significantly greater AL ratio at study completion compared to other groups (p < 0.05 all).ConclusionsResults are in support of the AL ratio as a measure of AT dysfunction among older adults. Furthermore, results suggest that a 12-month exercise and diet intervention with intentional weight loss assists in improving the AL ratio in this population.

Profile of insulin resistance in adipose tissue of diet induced obese mice in response to anti‐obesity treatment

BackgroundAdipose tissue is an insulin‐responsive organ that contributes to both glucose and lipid metabolism. Insulin resistance (IR) is when insulin‐dependent tissues lose their sensitivity to insulin, resulting in high blood glucose and insulin due to impairment of the negative feedback mechanism. Insulin resistance progress to metabolic disorders like obesity and type 2 diabetes. Sulforaphane (SFN) is a potential anti‐obesity drug under investigation.AimThis study aims to understand the effect of SFN on insulin resistance pathways in adipose tissues of diet induced obese (DIO) mice.MethodsWild‐type CD1 male mice were fed a high‐fat diet (HFD) for 16 weeks to induce obesity. Mice were divided into two groups DIO‐SFN and DIO‐V. DIO mice have been injected via IP route by SFN (5 mg/kg BW) or Vehicle (25μl) for 4 weeks. Daily body weight measurements have been recorded, and glucose tolerance test (GTT) at day 21 after injection and insulin tolerance test (ITT) at day 25 after injection. Subsequently, mice were sacrificed, blood and tissue samples were collected and snap‐frozen instantly. Total RNA was extracted from epididymal white adipose tissue (eWAT). Plasma leptin, insulin, and glucose level were measured, and 84 IR genes in adipose tissues were examined using RT‐PCR array technology.ResultsSFN treatment to DIO mice causes a significant reduction in body weight by 18.4%. Furthermore, SFN causes a significant reduction in circulating leptin concentrations in DIO‐SFN compared to the vehicle‐treated group. SFN is associated with the improvement of GTT and ITT. SFN causes dysregulation of eight genes related to inflammation, adipocytokine signaling, Il‐6, and HMGB1 pathways. SFN treatment causes significant changes in functions related to adipose tissue insulin resistance such as inhibition of chemotaxsis, inflammatory response and lipid accumulation.ConclusionThis study demonstrated that SFN treatment effectively reduces body weight and can ameliorate IR in eWAT via inhibition of pathways mainly related to inflammation, such as adipocytokine signaling, Il‐6, and HMGB1. SFN can be considered a future anti‐obesity drug.

Serum Thyroid Hormones Pictures in Non Thyroidal Illness Syndrome and Circulating Leptin Concentration in Patients with Uncontrolled Type 2 Diabetes Mellitus in a Group of Bangladeshi Population

Background: Thyroid diseases and diabetes mellitus are common endocrine disorders and Euthyroid Sick Syndrome is very common in uncontrolled type2 Diabetes Mellitus. As of thyroid hormones; the catabolic hormone Leptin is thought be closely linked with Diabetes Mellitus and Euthyroid Sick Syndrome. Objective: To evaluate the thyroid hormone pictures in absence of clinical thyroid diseases among type2 diabetic subjects in a Bangladeshi population. To see the baseline serum leptin concentration in a group of Bangladeshi adult population and to document how the leptin is related to glycemic status and Sick Euthyroid syndrome in the setting of uncontrolled type 2 Diabetes Mellitus. Method: This case and control study was carried out in the Endocrinology Department in collaboration with the Bio-Medical Research Group (BMRG), Research Division, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrinology and Metabolism (BIRDEM)), Dhaka, Bangladesh during the period of January 2000 to December 2002. A total of 100 type 2 diabetic subjects, 30-50 years of age, irrespective of glycemic status, duration of diabetes, Body Mass Index (BMI) and sex were recruited from the outpatient department (OPD) of BIRDEM hospital. Control subjects (n=30) were selected from friends and family of the patients within 5 years of age band without diabetes or impaired glucose regulation {Impaired Fasting Glycemia (IFG), Impaired Glucose Tolerance (IGT)} determined according to American Diabetic Association (ADA) criteria [37] and having no clinical thyroid diseases or other evident systemic diseases documented on clinical evaluation. Results: It was observed that mean± SD of the thyroid hormone pictures in diabetic and control subjects were; TT3 (ngm/dl) {in controls (88.91±15.88) and in diabetic subjects (84.27±22.29)} was not statistically significant to each other (p=0.209). Mean±SD of TT4 (µgm/ dl) in control subjects was 8.32±1.64 and in the diabetic subjects was 9.26±1.44, which is almost similar in both the groups (p= 0.589). FT4: (pgm/ml) in control subjects was 2.60±0.54 and in diabetics was 2.53±1.72 (p= 0.830). FT4. (µgm/ dl) in control subjects was 1.43±0.22 and in diabetics subjects 1.36±0.25. (p 0.179). TSH (µlu/ml) in control subjects was 1.34±1.00 and in diabetic subjects 1.54±1.21 (p: 0.411). FT3; FT4 and TSH showed no significant difference between control and diabetic subjects. Thyroid hormones (TT3, TT4, FT3, FT4) and TSH were reanalyzed according to HbA1c and BMI category and showed no significant differences. But when the FPG and HbA1c goes beyond 12 mmol/l and 10% respectively there was more worsening thyroid hormone pictures in comparison to groups whose FPG and HbA1c were below 12mmol/l and 10%. It was also noticed that there was a tendency to develop lower thyroid hormone pictures and more deteriorating glycemic status in patient with low and normal BMI groups in comparison to higher BMI groups of patients. Insulin and leptin were found to have strong positive correlation with BMI and other indices of obesity. Serum leptin was also found to be positively correlated with FPG and HbA1c upto a certain limit, but HbA1c went beyond 10%; serum leptin concentration tended to be declined. Serum leptin and Insulin showed strong positive correlation to each other’s. Thyroid hormones and TSH were re-analyzed and its relationship to FPG, HbA1c, fasting serum Insulin and Leptin were explored. Fasting serum Insulin and Leptin showed no significant differences among the different thyroid hormones groups. Conclusion: Uncontrolled type2 diabetes mellitus is associated with alteration of thyroid hormone pictures particularly affecting TT3, FT3 and TSH. This biochemical feature is more evident if the BMI of the Diabetic subjects is low or within the normal range and also the more worsening the glycemic status, there were more deteriorating serum thyroid hormone pictures. Serum leptin was not found to have any relation with these changes.

EFFECT OF LEPTIN CONCENTRATIONS AND LEPTIN RECEPTOR GENE POLYMORPHISMS ON THE OUTCOME OF RENAL TRANSPLANTATION

IntroductionLeptin is a pro-inflammatory adipocytokine implicated in cardiovascular disease, insulin resistance, obesity and chronic kidney disease.Material and methodsIn a cohort of 236 renal transplant recipients, we aimed to determine whether circulating leptin concentrations and/or three polymorphisms in the leptin receptor (LEPR) gene, namely rs1137100, rs1137101 and rs1805094, were related to clinical outcomes in renal transplantation. Plasma leptin concentrations were measured by ELISA. Genetic variants were determined by conventional real-time PCR assays and statistical associations with clinical outcomes were obtained by logistic regression modelling.ResultsPatients with elevated leptin levels were at higher risk of acute rejection [OR=1.03 (1.01–1.05), p=0.03] and displayed worse renal clearance (p=0.001) than patients with lower levels. Leptin levels were not significantly affected by any of the three LEPR SNPs. The rs1137101 G variant showed an inverse association with the risk of delayed graft function (DGF) [OR=0.42 (0.22-0.81), p=0.009], whilst the homozygous rs1805094 CC genotype was associated with increased risk of acute rejection [OR=11.38 (2.15-60.16), p=0.004]. A statistically significant association was also observed between the rs1137100 GG genotype and better renal function [mean difference vs. AA/AG =20.20 (4.91-35.49) ml/min, p=0.010].ConclusionsOur results show that both leptin plasma concentrations and polymorphisms in the LEPR gene may affect clinical outcomes in renal transplant recipients, suggesting that the determination of these parameters could be useful in predicting post-transplant adverse events.

60 Effects of exogenous glucocorticoid administration on leptin concentrations in perinatal dairy bull calves

Abstract Previous studies suggest a relationship between leptin and cortisol immediately postpartum is linked to improved feedlot efficiency on cattle exposed to perinatal stressors. The objective of the current study was to determine the effects of exogenous cortisol administration on circulating leptin concentrations in perinatal dairy bull calves. Within four hours of parturition, Holstein bull calves were randomly assigned to treatments and intravenously infused with low cortisol (LC; n =9, 3.5 ug/kg of cortisol), high cortisol (HC; n = 9, 7.0 ug/kg of cortisol), or a sham infusion control (CON; n = 9, similar volume of saline). Calves were housed similarly and fed milk replacer (28% CP, 20% fat) three times daily. Blood collections were performed via jugular venipuncture using Z/9mL serum collection tubes (Sarstedt, Newton, NC) from d 0 to 5 of age. Serum samples were incubated for 1 h at room temperature then overnight at 4°C, centrifuged at 1800 x g at 4°C for 20 minutes, serum decanted, and stored long term at -20°C until analysis. At 5 d of age, calves were euthanized utilizing an overdose of sodium pentobarbital (Schering-Plough Animal Health, Union, NJ) and cerebral-spinal fluid (CSF) from the third ventricle of the brain was collected and stored at -80°C until analysis. All samples were analyzed for leptin concentrations via a previously-validated radioimmunoassay. Serum leptin concentrations were analyzed via repeated measures of ANOVA and CSF leptin concentrations via the GLM procedure of SAS (SAS Institute Inc., Cary, NC, USA). Serum leptin concentrations of HC and LC were decreased (P = 0.013) compared to CON, and d 0 was decreased (P &amp;lt; 0.001) compared to all other days of age. Cerebral-spinal fluid leptin concentrations of HC and LC were decreased (P = 0.005) compared to CON. In summary, exogenous cortisol administered to perinatal dairy bull calves reduced leptin concentrations in serum and CSF.

59 Effects of exogenous glucocorticoid administration on leptin concentrations in perinatal dairy bull calves

Abstract Previous studies suggest a relationship between leptin and cortisol immediately postpartum is linked to improved feedlot efficiency on cattle exposed to perinatal stressors. The objective of the current study was to determine the effects of exogenous cortisol administration on circulating leptin concentrations in perinatal dairy bull calves. Within four hours of parturition, Holstein bull calves were randomly assigned to treatments and intravenously infused with low cortisol (LC; n = 9, 3.5 ug/kg of cortisol), high cortisol (HC; n = 9, 7.0 ug/kg of cortisol), or a sham infusion control (CON; n = 9, similar volume of saline). Calves were housed similarly and fed milk replacer (28% CP, 20% fat) three times daily. Blood collections were performed via jugular venipuncture using Z/9mL serum collection tubes (Sarstedt, Newton, NC) from d 0 to 5 of age. Serum samples were incubated for 1 h at room temperature then overnight at 4°C, centrifuged at 1800 x g at 4°C for 20 minutes, serum decanted, and stored long term at -20°C until analysis. At 5 d of age, calves were euthanized utilizing an overdose of sodium pentobarbital (Schering-Plough Animal Health, Union, NJ) and cerebral-spinal fluid (CSF) from the third ventricle of the brain was collected and stored at -80°C until analysis. All samples were analyzed for leptin concentrations via a previously-validated radioimmunoassay. Serum leptin concentrations were analyzed via repeated measures of ANOVA and CSF leptin concentrations via the GLM procedure of SAS (SAS Institute Inc., Cary, NC, USA). Serum leptin concentrations of HC and LC were decreased (P = 0.013) compared to CON, and d 0 was decreased (P &amp;lt; 0.001) compared to all other days of age. Cerebral-spinal fluid leptin concentrations of HC and LC were decreased (P = 0.005) compared to CON. In summary, exogenous cortisol administered to perinatal dairy bull calves reduced leptin concentrations in serum and CSF.

Differing planes of pre- and postweaning phase nutrition in Holstein heifers: II. Effects on circulating leptin, luteinizing hormone, and age at puberty

The objectives were to investigate the effects of differing planes of pre- and postweaning nutrition on prepubertal serum leptin concentrations, LH profiles, and age at puberty in Holstein heifers. Thirty-six Holstein calves were randomly assigned to either a low (5 L) or high (10 L of whole milk/d) preweaning plane of nutrition from 1 to 7 wk of age, a transition diet (a dry total mixed ration with 85% of concentrate) from wk 8 to 10, and to either a low (70%) or high (85% of concentrate dry total mixed ration) postweaning plane from 11 to 25 wk of age. Serum leptin concentrations were measured every 2 wk from 1 to 25 wk of age, and LH profiles were determined both at wk 15 and 25 based on sequential blood samples taken every 12 min over 10 h. Starting at 26 wk of age, ovaries were examined weekly by transrectal ultrasonography until first ovulation (puberty) was confirmed. Heifers that received the high preweaning plane diet had greater mean (± standard error; SE) leptin concentrations during the preweaning phase than those fed the low plane (2.9 ± 0.1 vs. 2.6 ± 0.1 ng/mL). During the postweaning phase, mean circulating leptin was greater in heifers fed the high compared with the low postweaning diet [3.2 ng/mL (95% confidence interval; CI = 2.7 to 3.4) vs. 2.5 ng/mL (95% CI = 2.3 to 2.8)]. Mean (± SE) amplitude (2.1 ± 0.1 vs. 1.7 ± 0.1 ng/mL), peak (2.2 ± 0.1 vs. 1.8 ± 0.1 ng/mL), and duration (35.6 ± 2.1 vs. 28.7 ± 2.0 min) of LH pulses assessed at wk 15 were greater in heifers offered the high than those offered the low preweaning plane, but no nutritional effects were observed on LH pulses at wk 25. Mean (± SE) age at puberty was 250 ± 9 d and was not influenced by planes of nutrition. However, the likelihood of attaining puberty by 30 wk of age was greater (hazard ratio = 3.8; 95% CI = 1.0 to 14.4) in heifers fed the high postweaning plane compared with the low plane. Heifers achieving puberty by 30 wk also had greater leptin concentrations from wk 1 to 25, whereas for every 1 ng/mL increase in circulating leptin at wk 15 and 25, days to puberty were estimated to decrease by 22 d (95% CI = 1 to 44) and 13 d (95% CI = 1 to 24), respectively. Increasing the preweaning plane from 5 to 10 L/d of whole milk increased serum leptin concentrations at wk 1, 3, and 5 and LH pulse amplitude, peak, and duration at wk 15. Increasing the postweaning plane from 70 to 85% of concentrate resulted in greater circulating leptin concentrations, which may be linked to an earlier onset of puberty.

Acetyl-CoA Regulation, OXPHOS Integrity and Leptin Levels Are Different in Females With Childhood vs Adulthood Onset of Obesity.

Although childhood-onset obesity (CO) and adulthood-onset obesity (AO) are known to lead to distinctive clinical manifestations and disease risks, the fundamental differences between them are largely unclear. The aim of the current study is to investigate the fundamental differences between subcutaneous adipose tissue from CO and AO and to identify metabolic differences between abdominal (abSAT) and femoral subcutaneous adipose tissues (feSAT). Total and regional body composition was assessed using dual-energy x-ray absorptiometry (DXA) and computed tomography. Levels of acetyl-CoA, NAD+/NADH, acetyl-CoA network genes, mitochondrial complex abundance, H3 acetylation were determined in biopsied abSAT and feSAT. Serum leptin and adiponectin were measured. Our results showed that acetyl-CoA was higher in subcutaneous adipose tissue from subjects with AO compared with CO. Multiple linear regression revealed that ATP citrate lyase was the only main effect affecting the level of acetyl-CoA. Circulating leptin concentrations was higher in AO. The increased level of acetyl-CoA was strongly associated with histone H3 acetylation, LEP expression in adipose tissue, and circulating leptin in AO. NAD+/NADH was higher in CO; however, abundance of mitochondrial complexes, the complex II:complex V ratio, and the complex IV:complex V ratio were lower in CO, reflecting compromised mitochondrial function in subcutaneous adipose tissue from CO. Moreover, we identified differences in the level of acetyl-CoA and NAD+/NADH ratio between abSAT and feSAT, suggesting that these fat depots may possess different metabolic properties. The fundamental difference in the important metabolic intermediate acetyl-CoA between CO and AO may help us better understand the development of obesity and the pathogenesis of different obesity-related diseases in humans.

Obesity, the most common comorbidity in SARS-CoV-2: is leptin the link?

Overweight and obesity are major risk factors for diabetes, cardiovascular disease, and lung disease. These diseases are the most commonly reported health conditions that predispose individuals with SARS-CoV-2 infection to require hospitalization including intensive care unit admissions. The innate immune response is the host’s first line of defense against a human coronavirus infection. However, most coronaviruses are armed with one strategy or another to overcome host antiviral defense, and the pathogenicity of the virus is related to its capacity to suppress host immunity. The multifaceted nature of obesity including its effects on immunity can fundamentally alter the pathogenesis of acute respiratory distress syndrome and pneumonia, which are the major causes of death due to SARS-CoV-2 infection. Elevated circulating leptin concentrations are a hallmark of obesity, which is associated with a leptin-resistant state. Leptin is secreted by adipocytes in proportion to body fat and regulates appetite and metabolism through signaling in the hypothalamus. However, leptin also signals through the Jak/STAT and Akt pathways, among others, to modulate T cell number and function. Thus, leptin connects metabolism with the immune response. Therefore, it seems appropriate that its dysregulation would have serious consequences during an infection. We propose that leptin may be the link between obesity and its high prevalence as a comorbidity of the SARS-CoV-2 infection. In this article, we present a synthesis of the mechanisms underpinning susceptibility to respiratory viral infections and the contribution of the immunomodulatory effects of obesity to the outcome.

Ovine prenatal growth-restriction and sex influence fetal adipose tissue phenotype and impact postnatal lipid metabolism and adiposity in vivo from birth until adulthood.

Adipose tissue development begins in utero and is a key target of developmental programming. Here the influence of nutritionally-mediated prenatal growth-restriction on perirenal adipose tissue (PAT) gene expression and adipocyte phenotype in late fetal life was investigated in both sexes in an ovine model. Likewise circulating leptin concentrations and non-esterified fatty acid (NEFA) and glycerol responses to glucose challenge were determined in relation to offspring adiposity at key stages from birth to mid-adult life. In both studies' singleton-bearing adolescent sheep were fed control or high nutrient intakes to induce normal or growth-restricted pregnancies, respectively. Fetal growth-restriction at day 130 of gestation (32% lighter) was characterised by greater body-weight-specific PAT mass and higher PAT expression of peroxisome proliferator-activated receptor gamma (PPARɤ), glycerol-3-phosphate dehydrogenase, hormone sensitive lipase (HSL), insulin-like growth factor 1 receptor, and uncoupling protein 1. Independent of prenatal growth, females had a greater body-weight-specific PAT mass, more multilocular adipocytes, higher leptin and lower insulin-like growth factor 1 mRNA than males. Growth-restricted offspring of both sexes (42% lighter at birth) were characterised by higher plasma NEFA concentrations across the life-course (post-fasting and after glucose challenge at 7, 32, 60, 85 and 106 weeks of age) consistent with reduced adipose tissue insulin sensitivity. Circulating plasma leptin correlated with body fat percentage (females>males) and restricted compared with normal females had more body fat and increased abundance of PPARɤ, HSL, leptin and adiponectin mRNA in PAT at necropsy (109 weeks). Therefore, prenatal nutrient supply and sex both influence adipose tissue development with consequences for lipid metabolism and body composition persisting throughout the life-course.