Hormone Leptin Research Articles

Adipokines: masterminds of metabolic inflammation.

Adipose tissue is an immunologically active organ that controls host physiology, partly through the release of mediators termed adipokines. In obesity, adipocytes and infiltrating leukocytes produce adipokines, which include the hormones adiponectin and leptin and cytokines such as tumour necrosis factor and IL-1β. These adipokines orchestrate immune responses that are collectively referred to as metabolic inflammation. Consequently, metabolic inflammation characterizes metabolic disorders and promotes distinct disease aspects, such as insulin resistance, metabolic dysfunction-associated liver disease and cardiovascular complications. In this unifying concept, adipokines participate in the immunological cross-talk that occurs between metabolically active organs in metabolic diseases, highlighting the fundamental role of adipokines in obesity and their potential for therapeutic intervention. Here, we summarize how adipokines shape metabolic inflammation in mice and humans, focusing on their contribution to metabolic disorders in the setting of obesity and discussing their value as therapeutic targets.

Evaluation of Adipose Tissue Hormones and Tumor Necrosis factor in Patients with Endometriosis

Objective: To evaluate levels of physiological parameters (Testosterone, follicle stimulating hormone FSH, luteinizing hormone LH, leptin and tumor necrosis factor TNF-α, Adipsin and Ghrelin), Total antioxidant capacity-TAC, Glutathione S transfers -GST in sera of patients with endometriosis. Method: This study involved (85) women within reproductive age (25-40) years, who were distributed into two groups: patientsʹ group (55) women diagnosed with endometriosis, and (30) healthy control women. The study was carried out at Al-Karkh Maternity Hospital/ Baghdad and extended from 20/4/2024 to 20/5/2024. The pathological cases of patients were diagnosed by clinical examinations and confirmed by specialist physician with ultrasound examination. Blood samples were taken from both groups, serum was separated for each individual by a centrifuge. Results: a significant rise in the (FSH, Leptin, TNF -α, Adipisin) while a significant decrease in levels of (Testosterone , LH, GST, TAC, Ghrelin) concentration were found in the sera of patients compered to healthy women , with a probability of P ≤ 0.05. According to Receiver operating characteristic (ROC) statistical analysis, Area under curve (AUC ) for LH, leptin, TNF -α, adipsin, ghrelin, GST, TAC were closely or equal to (1) for patients . Conclusion: serum levels of LH, Leptin, Adipisin, Gherlin, TNF-α and GST can be dependable as prognostic indicator markers that reflect the degree of oxidative stress accompanying endometriosis.

Roles of thyroid and leptin hormones and their crosstalk in male reproductive functions: an updated review.

This review aims to provide updated information regarding the role of thyroid and leptin hormones and their crosstalk in affecting the male reproductive function in hypothyroid and obesity conditions. A wide literature search was made using online search engines on published articles using keywords including thyroid hormone, hypothyroidism, leptin hormone, hyperleptinemia, obesity, the relationship between thyroid and leptin hormones and male reproduction, and hypothyroidism, obesity, and male reproduction. All information pertaining thyroid and leptin hormone effects on male reproduction, hypothyroidism, hyperleptinemia, and obesity effect on male fertility as well as the related molecular mechanisms are obtained. Thyroid and leptin hormones individually play a significant role in male reproduction. Alterations of these hormones' levels could adversely affect the male reproductive functions. PI3K/AKT signaling was found to be the major signaling pathway involved in mediating the effect of both hormones on male reproduction. Impaired crosstalk between the two hormones may occur in hypothyroidism with obesity which would contribute towards male reproductive dysfunction.

Relation between Serum Leptin, Lipid Profiles and other biomarkers levels in patients with type 2 diabetic nephropathy

Background: In advanced diabetes mellitus, serum levels of the most hormones are altered due to several interplaying mechanisms. Objective: To assess the relation of serum leptin and lipid profile in type 2 diabetic nephropathy. Patients and Method: Serum leptin levels and its relation to lipid profile were estimated in 62 patients with type 2 diabetic nephropathy attending the National Diabetes Center in Al- Mustansiriya University, and (26) healthy individuals considered as control group. The diabetic patients were classified into three groups, (24) pathients with normoalbuminuria (21) patients with microalbuminuria and (17) patients with macroalbuminuria. Fasting plasma glucose, serum creatinine, Hb A1c %, lipid profile (Total cholesterol, LDL- Cholesterol, HDL- Cholesterol and Triglyceride) and urinary albumin, were measured to establish the possibility of using these biomarkers as a supplementary to serum leptin to be a diagnostic test for type 2 diabetic nephropathy. Results: Serum leptin levels showed a significant elevation in microalbuminuria (20.08± 4.50 ng/ml) and macroalbuminuria groups (22.35± 6.89 ng/ml) as compared to nondiabetic normal control group (10.64 ± 3.17 ng/ml). There was no significant differences observed in serum leptin levels between the normoalbuminuria group (13.96 ± 5.73 ng/ml) and healthy controls, but a significant positive differences were noticed in the levels of fasting plasma glucose, serum creatinine, Hb A1c% and lipid profile in the three patient groups in comparison with the control group. While no significant correlation was observed between these biomarkers levels and serum leptin values. Conclusion: It might be concluded that serum leptin levels were elevated in type 2 diabetic patients with microalbuminuria and macroalbuminuria, suggesting that renal leptin degradation is impaired in early stage of kidney damage and this impairment increase with the progression of this disease. Leptin hormone may consider according to these results as a risk factor for progression of kidney disease in diabetic patients.

7788 Importance of Neuronal STAT3, but Not ERK2 or mTOR, for Pubertal Timing and Reproductive Activity in Mice

Abstract Disclosure: R.A. Lord: None. M.A. Inglis: None. G.M. Anderson: None. The adipose-derived hormone leptin is important for regulating reproduction. The canonical JAK2/STAT3 pathway is the best-characterised leptin receptor signalling pathway. Neural STAT3 deletion is known to cause obesity; however, its reproductive influence is less understood. This experiment investigated whether STAT3 knockout from brain neurons or AgRP neurons, a neuronal population necessary for normal pubertal timing and reproduction, would unveil the necessity of STAT3 in reproductive function. We also tested the role of ERK2 and mTOR, two alternative leptin signalling molecules.Transgenic mice with a neuronal knockout were created via the Cre-loxP system. CamKinaseIIα-Cre mice were crossed with STAT3, mTOR or ERK2 floxed mice. AgRP-Cre mice were crossed with STAT3 floxed mice for STAT3 knockout in AgRP neurons. All groups were compared to Cre-negative littermate controls (n=6-12/group). Puberty onset was assessed post-weaning by examining genitalia development. Reproductive cyclicity and organ weights were measured in adults. Metabolic effects were evaluated through body weight, abdominal fat and fasting glucose measurements. Brain tissue analysis evaluated cellular responses to leptin for STAT3, ERK2, and mTOR. Data presented as mean ± SEM.Mice with ERK2 KO or mTOR KO showed no reproductive or metabolic deficits compared to controls. In marked contrast, neuronal STAT3 KO mice showed significantly increased body weight by 5 weeks of age and a 6-fold increase in abdominal adiposity as adults (both p<0.001 using two-way ANOVA and Student’s t-test respectively) compared to controls. Males had a significant 5-day delay in age at preputial separation (KO: 32.1±2.09 d; Control: 26.8±0.45 d, p<0.01, Student’s t-test) while females had a significant 7-day delay in vaginal opening (KO: 33.0±1.85 d, Control: 26.6±0.37 d, p<0.05, Student’s t-test), a 9-day delay in first estrus (KO: 37.8±1.89 d; Control: 29.4±0.65 d, p<0.01, Student’s t-test) and pronounced acyclicity. Neuronal STAT3 KO mice also had a >2-fold elevation in fasting glucose levels (p<0.001, Student’s t-test) and regressed reproductive organs. Female mice with STAT3 knockout in AgRP neurons showed significantly increased body weight (by 3 weeks [p<0.001], two-way ANOVA) and a significant 3-day delay in first estrus (KO: 31.1±0.71 d, Control: 28.6±0.45 d, p<0.01, Student’s t-test). These data show that neuronal STAT3 is critical for correctly timed puberty and subsequent fertility in male and female mice, whereas mTOR and ERK2 are not essential. These results have prompted a re-evaluation of previous conclusions about the role of STAT3 from experiments using LepR-Cre mice. Additionally, AgRP neuronal requirements for STAT3 exactly recapitulate AgRP requirements for leptin receptors. A better grasp of leptin signalling pathways will improve our understanding of how infertility arises due to metabolic disease. Presentation: 6/3/2024

7255 Tirzepatide Helps Achieve Glycemic Control and Lower Triglycerides in Seven Patients with Lipodystrophy

Abstract Disclosure: R. Meral: None. E.D. Frontera: None. M. Celik Guler: None. M.C. Foss de Freitas: None. N. Nachawi: None. D.T. Broome: Consulting Fee; Self; Tayco, Inc.. Research Investigator; Self; Novo Nordisk, Fractyl Laboratories, Rhythm Pharmaceuticals. S.I. Taylor: None. E.A. Oral: Advisory Board Member; Self; Amryt, Regeneron Pharmaceuticals. Consulting Fee; Self; Regeneron Pharmaceuticals, Amryt, Third Rock Ventures. Grant Recipient; Self; Regeneron Pharmaceuticals, Amryt. Research Investigator; Self; Novo Nordisk, Fractyl, Ionis Pharmaceuticals Inc., GI Dynamics, Rhythm Pharmaceuticals. Other; Self; Amryt. Lipodystrophy encompasses a group of rare disorders associated with severe metabolic disease. These disorders are defined by abnormal distribution of fat, with near-total (generalized lipodystrophy, GL) or partial (partial lipodystrophy, PL; i.e. familial partial lipodystrophy, FPLD) absence of adipocyte mass leading to a decreased ability to store triglycerides safely. Excess triglycerides are more likely to be stored in ectopic tissues such as hepatocytes, which leads to the metabolic manifestations of the disease state. Patients with GL have near absent levels of leptin hormone and leptin replacement therapy leads to dramatic improvement, which has mainly been attributed to a reduction in caloric intake. Patients with PL are not as leptin deficient and their response to leptin replacement therapy has been variable. We hypothesized that the clinical use of tirzepatide in patients with lipodystrophy may lead to favorable outcomes through the reduction of caloric intake. We closely observed 7 patients who were prescribed tirzepatide for their diabetes with information presented respectively [Age: 44; 54; 34; 53; 44; 46; 38 years | Sex: F; F; F; F; F; M; F | Subtype: FPLD type 1; FPLD type 2; FPLD type 1; Acquired GL; FPLD type 2; FPLD type 1; FPLD type 3]. At baseline, all patients had poor control of their disease despite aggressive medical therapy (except patient #5). Follow-up durations varied due to the observational nature of the study [follow-up duration (months): 6; 12; 7; 3; 8; 9; 5]. Reductions in A1c, triglycerides, and body mass index (BMI) were observed [A1c (%): 13.4->7.1; 7.1->6.6; 7.6->5.2; 8.7->6.9; 5.4->5.1; 8.9->7.8; 9.7->7.1 | triglycerides (mg/dL): 539->339; 164->109; 367->NA; 151->113; 388->101; 459->319; 4081->259 | BMI (Kg/m2): 25.0->24.5; 30.6->28.3; 37.7->33.9; 22.8->20.9; 27.6->23.4; 40.1->37.9; 24.0->24.9]. Those who were on insulin had decreased daily requirements [total daily insulin requirement (units): 160->25; 82->18; not on insulin; 85->0; not on insulin; 280->200; 124->111]. All patients reported a reduction in their daily food intake. Treatment related complications were limited to known gastrointestinal issues which the patients rated as tolerable. Based on our results, a randomized controlled trial to test the efficacy of tirzepatide in patients with lipodystrophy may be warranted. Presentation: 6/3/2024

Nutrition, Growth, and Age at Puberty in Heifers

Puberty onset and age at first calving have a critical impact on livestock production for good reproductive efficiency of the herd and to reduce the duration of the non-productive stage of the growing heifer. Besides genetic factors, sexual maturation is also affected by environmental factors, such as nutrition, which can account for up to 20% of the observed variability. The rate of body weight gain during growth is considered the main variable influencing the age at puberty, dependent on planes of nutrition in growing animals during the prepubertal-to-pregnancy stage. This paper reviews current knowledge concerning nutrition management and attainment of puberty in heifers, considering the relevance of some indicators such as body measurements and hormones strictly linked to the growth and puberty process. Puberty onset is dependent on the acquisition of adequate subcutaneous adipose tissue mass, as it is the main source of the hormone leptin. Until a certain level, body condition score and age at puberty are negatively correlated, but beyond that, for fatter animals, such correlation is gradually lost. Age at puberty in heifers was reported to be negatively related to IGF-1. Future research should be planned considering the need to standardize the experimental animals and conditions.

The Transcriptome Characterization of the Hypothalamus and the Identification of Key Genes during Sexual Maturation in Goats.

Sexual maturation in goats is a dynamic process regulated precisely by the hypothalamic-pituitary-gonadal axis and is essential for reproduction. The hypothalamus plays a crucial role in this process and is the control center of the reproductive activity. It is significant to study the molecular mechanisms in the hypothalamus regulating sexual maturation in goats. We analyzed the serum hormone profiles and hypothalamic mRNA expression profiles of female goats during sexual development (1 day old (neonatal, D1, n = 5), 2 months old (prepuberty, M2, n = 5), 4 months old (sexual maturity, M4, n = 5), and 6 months old (breeding period, M6, n = 5)). The results indicated that from D1 to M6, serum hormone levels, including FSH, LH, progesterone, estradiol, IGF1, and leptin, exhibited an initial increase followed by a decline, peaking at M4. Furthermore, we identified a total of 508 differentially expressed genes in the hypothalamus, with a total of four distinct expression patterns. Nuclear receptor subfamily 1, group D, member 1 (NR1D1), glucagon-like peptide 1 receptor (GLP1R), and gonadotropin-releasing hormone 1 (GnRH-1) may contribute to hormone secretion, energy metabolism, and signal transduction during goat sexual maturation via circadian rhythm regulation, ECM receptor interactions, neuroactive ligand-receptor interactions, and Wnt signaling pathways. This investigation offers novel insights into the molecular mechanisms governing the hypothalamic regulation of goat sexual maturation.

Abstract 68: Soluble FMS-Like Tyrosine Kinase 1 induces Vascular Endothelial Dysfunction in Pregnant Female Mice

Preeclampsia (PE) is a hypertensive disorder of pregnancy clinically characterized by hypertension and increased risk of fetal growth restriction. Elevated levels of anti-angiogenic soluble fms-like tyrosine kinase 1 (sFlt-1) is a well-known hallmark of PE. In addition, emerging clinical evidence indicates that vascular endothelial dysfunction is a mediator of PE. Although these two facets of PE are associated, whether sFlt-1 is a crucial mediator in endothelial dysfunction in PE is unknown. We previously showed that the placenta-derived hormone leptin, whose levels characteristically increase in PE patients, induces the features of PE in pregnant mice, notably endothelial dysfunction. Novel preliminary data also shows that sFlt-1 induces an increase in placental leptin production, however, what remains to be explored is whether this pathway mediates endothelial dysfunction in PE pregnant mice. Therefore, we hypothesize that in pregnant mice, sFlt-1 induces vascular endothelial dysfunction via increasing leptin production. We bred BALB/c female mice for timed pregnancy (12-14 wk old). On gestational day (GD)11, pregnant females were implanted with subcutaneous (sc.) minipumps containing either sFlt-1 (1.2 µg/day, n=5) or saline (n=6). Uterine artery resistance index (UARI) was measured at GD17 via Doppler ultrasound. At GD18, vascular reactivity was measured in 2nd-order mesenteric arteries by wire myography. Our data showed that sFlt-1 increased UARI compared to sham mice ([PSV-EDV]/PSV; Mean±SEM;0.61±0.01 vs. 0.45±0.01, t test, p=0.0007). In addition, sFlt-1 reduced endothelial-dependent relaxation to acetylcholine (concentration-response, 1nM-10µM, 2-way ANOVA w/RM, p<0.0001), indicating endothelial dysfunction. sFlt-1 also reduced smooth muscle relaxation responses to sodium nitroprusside (p<0.05). To test whether sFlt-1 induces leptin production, we bred BALB/c mice as described above. At GD12, mice were treated with either sFlt-1 (sc.10 µg) or saline (n=6/group). After 24 h, mice were euthanized, and plasma and subcutaneous adipose tissue were collected. Our data showed an increase in plasma leptin in sFlt-1 group (ng/mL;5.0 ±0.2 vs. 2.9±0.1, t test, p<0.0001) and an upregulation in placental leptin gene expression (normalized to 18S; fold change to control; 7.8±1.8 vs. 1.1±0.3, t test, p<0.05). In conclusion, our data indicates that sFlt-1 induces vascular endothelial dysfunction and increases leptin plasma levels and gene expression in preeclampsia.

Leptin signalling altered in infantile nephropathic cystinosis-related bone disorder.

The CTNS gene mutation causes infantile nephropathic cystinosis (INC). Patients with INC develop Fanconi syndrome and chronic kidney disease (CKD) with significant bone deformations. C57BL/6 Ctns-/- mice are an animal model for studying INC. Hyperleptinaemia results from the kidney's inability to eliminate the hormone leptin in CKD. Ctns-/- mice have elevated serum leptin concentrations. Leptin regulates bone metabolism through its receptor that signals further via the hypothalamic melanocortin 4 receptor (MC4R). Leptin signalling may affect bone health in Ctns-/- mice. We first defined the time course of bone abnormalities in Ctns-/- mice between 1 and 12months of age. We used both genetic and pharmacological approaches to investigate leptin signalling in Ctns-/- mice. We generated Ctns-/-Mc4r-/- double knockout mice. Bone phenotype of Ctns-/-Mc4r-/- mice, Ctns-/- mice and wild type (WT) mice at 1, 4, and 9months of age were compared. We then treated 12-month-old Ctns-/- mice and WT mice with a pegylated leptin receptor antagonist (PLA) (7mg/kg/day, IP), a MC4R antagonist agouti-related peptide (AgRP) (2nmol, intracranial infusion on days 0, 3, 6, 9, 12, 15, 18, 21, 24, and 27), or vehicle (normal saline), respectively, for 28days. Whole-body (BMC/BMD, bone area) and femoral bone phenotype (BMC/BMD, bone area, length and failure load) of mice were measured by DXA and femoral shaft biochemical test. We also measured lean mass content by EchoMRI and muscle function (grip strength and rotarod activity) in mice. Femur protein content of JAK2 and STAT3 was measured by ELISA kits, respectively. Bone defects are present in Ctns-/- mice throughout its first year of life. The deletion of the Mc4r gene attenuated bone disorder in Ctns-/- mice. Femoral BMD, bone area, length, and strength (failure load) were significantly increased in 9-month-old Ctns-/-Mc4r-/- mice than in age-matched Ctns-/- mice. PLA and AgRP treatment significantly increased femoral bone density (BMC/BMD) and mechanical strength in 12-month-old Ctns-/- mice. We adopted the pair-feeding approach for this study to show that the protective effects of PLA or AgRP on bone phenotype are independent of their potent orexigenic effect. Furthermore, an increase in lean mass and in vivo muscle function (grip strength and rotarod activity) are associated with improvements in bone phenotype (femoral BMC/BMD and mechanical strength) in Ctns-/- mice, suggesting a muscle-bone interplay. Decreased femur protein content of JAK2 and STAT3 was evident in Ctns-/- mice. PLA or AgRP treatment attenuated femur STAT3 content in Ctns-/- mice. Our findings suggest a significant role for dysregulated leptin signalling in INC-related bone disorder, either directly or potentially involving a muscle-bone interplay. Leptin signalling blockade may represent a novel approach to treating bone disease as well as muscle wasting in INC.

Generation of LEPR Knockout Rabbits with CRISPR/CAS9 System.

The LEPR gene encodes a leptin hormone receptor, and its mutations are associated with morbid obesity, dysregulation of lipid metabolism, and fertility defects in humans. Spontaneous Lepr mutations have been described in rodents, and Lepr knockout animals have been generated, in particular, using the CRISPR/Cas9 system. Lipid metabolism in rodents significantly differs from that in humans or rabbits, and rabbits are therefore considered as the most relevant model of morbid obesity and lipid metabolism dysregulation in humans. LEPR knockout rabbits have not been reported so far. In this work a LEPR knockout rabbit was generated by introducing a deletion of the region around LEPR exon 10 using the CRISPR/Cas9 system. The body weight of the knockout rabbit was significantly higher than the average body weight of the wild type rabbits. CRISPR/Cas9-mediated generation of LEPR knockout rabbits will allow the development of a model of morbid obesity and endocrine defects due to leptin receptor mutations in humans.

Elucidating the effect of dietary neem (Azadirachta indica) on growth performance, haemato-biochemical, immunonological response, and anti-pathogenic capacity of Nile tilapia juveniles.

This investigation attempts to evaluate the effect of diet additives via aqueous or ethanolic herbal extracts from Azadirachta indica leaves on Nile tilapia, Oreochromis niloticus. Five dietary categories were assigned to the fish: the first category (N1, with no extract) was kept under control conditions; two categories contained aqueous extract (N2 (1.0g/kg) and N3 (2.0g/kg); and two categories contained ethanolic extract, N4 (1.0g/kg) and N5 (2.0g/kg), with each group being fed for 60 days. After the feeding trial, Aeromonas hydrophila was injected intraperitoneally into fish for 14 days; fish mortality was recorded during this period. The results showed that the fish-fed dietary A. indica significantly improved growth performance and intestinal health (digestive enzymes and intestinal morphology), especially in the N4 and N5 categories. However, N4 and N5 categories demonstrated a significant decrease in AST and ALT activities and an increase in total protein, serum albumin, globulin, growth hormone (GH), leptin hormone (LEP), hemoglobin, white blood cells, and hematocrit (P < 0.05) in comparison with the control category (N1). Compared to the control category, the N4 and N5 categories have revealed a significant reduction in MDA activity and improvements in immunological activities (lysozyme, complement C3, and nitric oxide) and antioxidant enzymes (CAT, SOD, and GPX). Moreover, in tilapia-fed A. indica, the expression of IL-8, IL-1β, and Nf-κb genes was downregulated partially in the N4 and N5 categories than the control category. In contrast, the lysozyme, C3, GPX, and CAT genes were upregulated partially at N4 and N5 compared to the control category. Following the bacterial challenge, fish in the N4 and N5 categories also displayed the lowest fish mortality compared to the control category. The ethanolic extract displayed a more potent resistance against the parasite Cichlidogyrus tilapia in vitro than the aqueous and control categories, partially at 2g/L. According to these findings, an ethanolic neem extract (2.0g/kg feed) activates the immune system and antioxidant response in Nile tilapia fingerlings, improving growth and fish resistance to parasitic and bacterial infections.

Peripheral and seminal biochemical profiles in relation to sperm kinematics across seasons in buffalo bulls

ABSTRACT The correlation between peripheral and seminal hormones and biochemical parameters with sperm kinematics across seasons in buffalo bulls were studied. Semen from buffalo bulls (n = 13) during different seasons viz. summer, comfort (spring and autumn) and winter was collected. Sperm kinematics of ejaculates (n = 39) (three ejaculates per bull) were carried out during each season and simultaneously blood (10 mL) was collected and serum was separated for hormones (leptin, testosterone and kisspeptin) and biochemical [heat shock protein 70 (HSP70), ascorbic acid and total antioxidant capacity] estimation. Total motility (TM, %), progressive motility (PM, %) and rapid motility (RM, %) showed significant differences across seasons with the highest TM, PM and RM during winter. HSP70 was higher in seminal plasma levels during summer and TAC was higher in serum than seminal plasma during all seasons. In conclusion, seminal leptin and ascorbic acid showed an association with sperm kinematics across seasons in buffalo bulls.

Metabolism: Secretory autophagy balances nutrient supply and demand

The hormone leptin is critical for regulation of food intake, energy expenditure and overall metabolism. However, the mechanisms that promote leptin secretion from adipocytes in response to nutrient surplus and limit its secretion during nutrient scarcity are unclear. New work reveals that the autophagy protein Atg8/LC3 has a bidirectional role in leptin secretion, both facilitating and limiting its release.

Does gastric tissue Ghrelin and Leptin correlate with serum values? A pilot study of the Indian Obese population

BackgroundWhile serum Ghrelin and leptin has been studied over the last decades, there are very few human studies correlating the serum levels with the presence of the ghrelin and leptin cells in gastric tissue. MethodsWe have assessed the presence of leptin and ghrelin cells in the resected sleeve of stomach following Laparoscopic Sleeve Gastrectomy (LSG) and correlated the same with serum levels of ghrelin and leptin hormones before and after 6 months of surgery. The study was conducted at department of gastro-intestinal (GI) surgery of a tertiary care hospital from 2017–2019. ResultsForty-five patients participated in the study. Thirty-five of the specimens were negative for ghrelin cells and 29 were negative for leptin cells. While the levels of serum ghrelin in the ghrelin-negative specimen group were lower than normal, the levels in the ghrelin-positive specimen group were significantly higher, which reduced following LSG. In the leptin group, while the leptin-positive group had higher serum levels that dropped after surgery, the leptin-negative group also showed raised serum leptin levels, which further increased after surgery. Serum ghrelin levels showed a positive correlation with serum insulin levels but did not translate to statistically significant increased number of diabetic patients. ConclusionGhrelin and leptin cells are not universally present in the stomach in Indian population. Serum values of leptin and ghrelin correlates positively to the presence of their secreting cells in the Gastric sleeve. This study gives scope to evaluate the presence and distribution of these cells in the gastric sleeve.

Resting Energy Expenditure, Metabolic and Sex Hormones in Two Phases of the Menstrual and Hormonal Contraceptive Cycles.

Resting energy expenditure (REE) may fluctuate during the menstrual cycle (MC), due to the physiological effects of estradiol (E2) and progesterone (P4). This study examined changes in REE and metabolic hormones (leptin, ghrelin, thyroid hormones), and dietary intake in two hormonally distinct groups, naturally menstruating women (NoOC) and women using monophasic combined oral contraceptives (COC). Measurements included REE by indirect calorimetry, body composition by bioimpedance, and blood samples for hormone analysis in the early follicular and mid-luteal phases of the MC in NoOC-group (n = 38) or the active and inactive phases of the COC cycle (COC, n = 19). Participants recorded their food intake for 3 days after measurements. A secondary analysis was completed for the NoOC-group without REE outliers (difference between measurements >1.5 × interquartile range, n = 4). In the NoOC-group, luteal phase REE was 40 kcal higher than follicular phase REE [95% confidence interval (CI): -2 kcal/d-82 kcal/d, d = 0.20, p = 0.061]. Leptin (d = 0.35, p < 0.001), T3 (d = 0.26, p = 0.05) and fat intake (d = 0.48, p = 0.027) were lower, and T4 (d = 0.21, p = 0.041) was higher in the luteal phase. After excluding outliers, REE was 44 kcal higher in the luteal phase than in the follicular phase (95% CI: 12 kcal/d-76 kcal/d, d = 0.22, p = 0.007). In the COC-group, the mean difference in REE was -2 kcal (95% CI-82 kcal/d-79 kcal/d) between active and inactive phases, while T3 was higher in the inactive phase (d = 0.01, p = 0.037). REE increases only slightly from the follicular to the luteal phase but remains unchanged between COC phases. Increases in T3, leptin, and fat intake during the luteal phase might echo metabolic fluctuations that parallel female sex hormones during the MC.

Investigation of some fertility indicators in Iraqi women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a complex, heterogeneous, multigenic disorder in women of childbearing age with multiple consequences. The exact mechanism of PCOS is not yet fully understood; There are several factors have a role such as genetic, environmental, nutritional, metabolic and other interactions Therefore, the existing study designed to estimate the levels of some biochemical tests and the sex hormones that have a role in PCOS progress. 100 Iraqi women were agreed to participate in the current study, divided into two groups included 50 clinically diagnosed with PCOS women that compared with 50 healthy women without PCOS as a control group (CTRL). The results showed different significant differences of the studied parameters between the PCOS and the CTRL. There was a significant increased level of FBG, HbA1c, insulin resistant, TG and LDL in the PCOS group in comparison to the CTRL, while a significant decreased level of HDL was appeared in PCOS group in comparison to the CTRL. Regarding the results of sex hormones, there were significant increased levels of LH, FSH, testosterone, estradiol hormones in the PCOS group in comparison to the CTRL. In addition, the results of thyroid hormones appeared a significant increased level of T3 hormone in the PCOS group in comparison to the CTRL. Also, the results of leptin hormone showed a significant increased level in the PCOS group in comparison to the CTRL. In conclusion, there was a significant relationship between FBG, HbA1c, insulin resistant, TG, LDL, HDL, LH, FSH and T3 parameters with PCOS.

A quantitative pipeline to assess secretion of human leptin coding variants reveals mechanisms underlying leptin deficiencies

The hormone leptin, primarily secreted by adipocytes, plays a crucial role in regulating whole-body energy homeostasis. Homozygous loss-of-function mutations in the leptin gene (LEP) cause hyperphagia and severe obesity, primarily through alterations in leptin's affinity for its receptor or changes in serum leptin concentrations. Although serum concentrations are influenced by various factors (e.g., gene expression, protein synthesis, stability in the serum), proper delivery of leptin from its site of synthesis in the endoplasmic reticulum via the secretory pathway to the extracellular serum is a critical step. However, the regulatory mechanisms and specific machinery involved in this trafficking route, particularly in the context of human LEP mutations, remain largely unexplored.We have employed the Retention Using Selective Hooks (RUSH) system to elucidate the secretory pathway of leptin. We have refined this system into a medium-throughput assay for examining the pathophysiology of a range of obesity-associated LEP variants. Our results reveal that leptin follows the default secretory pathway, with no additional regulatory steps identified prior to secretion.Through screening of leptin variants, we identified three mutations that lead to proteasomal degradation of leptin and one variant that significantly decreased leptin secretion, likely through aberrant disulfide bond formation. These observations have identified novel pathogenic effects of leptin variants, which can be informative for therapeutics and diagnostics. Finally, our novel quantitative screening platform can be adapted for other secreted proteins.

Novel Leptin-Based Therapeutic Strategies to Limit Synaptic Dysfunction in Alzheimer's Disease.

Accumulation of hyper-phosphorylated tau and amyloid beta (Aβ) are key pathological hallmarks of Alzheimer's disease (AD). Increasing evidence indicates that in the early pre-clinical stages of AD, phosphorylation and build-up of tau drives impairments in hippocampal excitatory synaptic function, which ultimately leads to cognitive deficits. Consequently, limiting tau-related synaptic abnormalities may have beneficial effects in AD. There is now significant evidence that the hippocampus is an important brain target for the endocrine hormone leptin and that leptin has pro-cognitive properties, as activation of synaptic leptin receptors markedly influences higher cognitive processes including learning and memory. Clinical studies have identified a link between the circulating leptin levels and the risk of AD, such that AD risk is elevated when leptin levels fall outwith the physiological range. This has fuelled interest in targeting the leptin system therapeutically. Accumulating evidence supports this possibility, as numerous studies have shown that leptin has protective effects in a variety of models of AD. Recent findings have demonstrated that leptin has beneficial effects in the preclinical stages of AD, as leptin prevents the early synaptic impairments driven by tau protein and amyloid β. Here we review recent findings that implicate the leptin system as a potential novel therapeutic target in AD.

Atg8/LC3 controls systemic nutrient surplus signaling in flies and humans

Organisms experience constant nutritional flux. Mechanisms at the interface of opposing nutritional states-scarcity and surplus-enable organismal energy homeostasis. Contingent on nutritional stores, adipocytes secrete adipokines, such as the fat hormone leptin, to signal nutrient status to the central brain. Increased leptin secretion underlies metabolic dysregulation during common obesity, but the molecular mechanisms regulating leptin secretion from human adipocytes are poorly understood. Here, we report that Atg8/LC3 family proteins, best known for their role in autophagy during nutrient scarcity, play an evolutionarily conserved role during nutrient surplus by promoting adipokine secretion. We show that in a well-fed state, Atg8/LC3 promotes the secretion of the Drosophila functional leptin ortholog unpaired 2 (Upd2) and leptin from human adipocytes. Proteomic analyses reveal that LC3 directs leptin to a secretory pathway in human cells. We identified LC3-dependent extracellular vesicle (EV) loading and secretion (LDELS) as a required step for leptin release, highlighting a unique secretory route adopted by leptin in human adipocytes. In Drosophila, mutations to Upd2's Atg8 interaction motif (AIM) result in constitutive adipokine retention. Atg8-mediated Upd2 retention alters lipid storage and hunger response and rewires the bulk organismal transcriptome in a manner conducive to starvation survival. Thus, Atg8/LC3's bidirectional role in nutrient sensing-conveying nutrient surplus and responding to nutrient deprivation-enables organisms to manage nutrient flux effectively. We posit that decoding how bidirectional molecular switches-such as Atg8/LC3-operate at the nexus of nutritional scarcity and surplus will inform therapeutic strategies to tackle chronic metabolic disorders.