Human Leptin Research Articles

Leptin increases hepatic triglyceride export via a vagal mechanism in humans

Recombinant human leptin (metreleptin) reduces hepatic lipid content in patients with lipodystrophy and overweight patients with non-alcoholic fatty liver disease and relative hypoleptinemia independent of its anorexic action. In rodents, leptin signaling in the brain increases very-low-density lipoprotein triglyceride (VLDL-TG) secretion and reduces hepatic lipid content via the vagus nerve. In this randomized, placebo-controlled crossover trial (EudraCT Nr. 2017-003014-22), we tested whether a comparable mechanism regulates hepatic lipid metabolism in humans. A single metreleptin injection stimulated hepatic VLDL-TG secretion (primary outcome) and reduced hepatic lipid content in fasted, lean men (n= 13, age range 20-38 years) but failed to do so in metabolically healthy liver transplant recipients (n= 9, age range 26-62 years) who represent a model for hepatic denervation. In an independent cohort of lean men (n= 10, age range 23-31 years), vagal stimulation by modified sham feeding replicated the effects of metreleptin on VLDL-TG secretion. Therefore, we propose that leptin has anti-steatotic properties that are independent of food intake by stimulating hepatic VLDL-TG export via a brain-vagus-liver axis.

INVESTIGATION OF 2548G>A LEPTINE GENE POLYMORPHIC VARIANT IMPACT ON RISK OF NON-ALCOHOLIC FATTY LIVER DISEASE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Background. It is known that single nucleotide polymorphisms (SNPs) in adipokine genes can influence the development of pathological conditions associated with obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease and their complications. In this study, we aimed to investigate the link between common -2548G>A (rs7799039) promoter variant of the human leptin gene (LEP) with leptin levels in type 2 diabetes patients with non-alcoholic fatty liver diseasese. Materials and methods. 61 patients with T2D aged from 28 to 80 years old (34 men/27 women, age 56.40±0.62 yrs, diabetes duration 7.72±0.45 yrs, BMI 32.20±0.43 kg/m2, WHR 1,00 ±0,01, HbA1c 7.80±0.19 %) with varying degrees of glycemic control and overweight, without renal insufficiency and 51 sex and age-match control subjects were examined. Genotyping according to SNP LEP 2548G>A was performed using the polymerase chain reaction method with appropriate primers and HhaI endonuclease. Results. In our study of T2DM patients with NAFLD compared to T2DM patients without NAFLD features of dyslipidemia i.e. significant increase in triglycerides (p <0,001), LDL cholesterol (p <0,1), lower HDL cholesterol ( p <0.001) were found. Stratification of the diabetic patients in the presence and absence of NAFLD showed more pronounced increase in circulating leptin levels in the presence of NAFLD (84.73 ± 13.80 vs. 52.57 ± 6.86 ng / ml, respectively), (p <0.01), which justifies the feasibility of using this indicator for further needs as a diagnostic parameter of the above complication. In our study in GG carriers genotype of the G2548A LEP gene polymorphic locus type 2 diabetes patients with NAFLD the highest level of leptin was observed (159.15 ng/ml), compared to other genotypes. Thus, it can be assumed that the G allele is associated with increased leptin levels in the blood of patients with NAFLD. This study showed that women with type 2 diabetes mellitus carrying the GG genotype with the G-2458A polymorphic variant of the LEP gene have 3.4 times higher leptin levels than men carrying the same genotype (p<0.03). The data obtained regarding the 2548G>A polymorphic variant of the LEP gene can be used as a basis for personalized prevention and the formation of risk groups for the development of NAFLD.

Effects of tramadol abuse on plasma concentration of leptin and agouti related protein (AgRP)

The current study is a trial to understand the effect of one of the most commonly used analgesics and also one of the most abused drugs “tramadol” on the hormones regulating the appetite and subsequently the body weight “Leptin and AgRP”. This study included 40 participants, classified into four groups, 10 participants each. Group I (GI) and group II (GII) composed of control healthy volunteer males having confirmed negative tramadol and des-methy-tramadol in their blood. GI participants aged 38.67 ± 2.35 years and have normal weight with Body Mass Index (BMI) equal 21.9 ± 0.67. GII participants aged 37.40 ± 2.67 years and having BMI equal 33.93 ± 0.57. Group III (GIII) and group IV (GIV) had positive tramadol and des-methyl- tramadol in their blood confirmed by gas chromatography-mass spectrometry. GIII participants have normal weight with BMI equal 22.55 ± 0.88 and age equal 37.66 ± 2.30 years. GIV participants were obese with BMI equal 33.83 ± 0.81 and age equal to 36.40 ± 2.60 years. All subjects with hypertension and diabetes mellitus were excluded. Human leptin hormone was measured depending on immunoradiometric assay IRMA; the human AgRP hormone was measured by using a quantitative sandwich enzyme immunoassay technique. Leptin concentration in obese non tramadol users (GII) is increased (14.78 ± 0.74) in comparison to the normal weight non tramadol users (GI) (6.96 ± 0.43) but it is lower than the obese tramadol users (GIV) (17.68 ± 0.6) while the normal weight tramadol users (GIII) showed increased leptin concentration (14.02 ± 0.83) in comparison to the normal weight non tramadol users (GI) (6.96 ± 0.43) and decreased leptin concentration in comparison to the obese tramadol users (GIV) (17.68 ± 0.6). Regarding the blood concentration of AgR P, it was higher in GII (17.12 ± 1.14) than GIV (11.85 ± 0.79) and lower in GIII (17.33 ± 0.98) than GI (25.05 ± 0.72). So it can be concluded that using tramadol was associated with an increase in leptin concentration either on comparing the normal weight groups or the high BMI groups. An opposite effect was seen on AgRP concentration. There is positive correlation between leptin and BMI in the control groups (GI and GII) and negative correlations in the tramadol users in groups (GIII and GIV) meanwhile there was a negative correlation between AgRP and BMI in the control groups (GI and GII) and positive correlations in the tramadol users in groups (GIII and GIV). A negative correlation between leptin and AgRP in all the studied groups. It is concluded that tramadol abuses increased leptin concentration in both normal weight and obese cases in comparison to non-abusers either normal weight or obese. Meanwhile, it decreased AgRP concentration in both normal weight and obese cases in comparison to non-abusers either normal weight or obese. Also, the review of the literature concluded that they are also altered in different cases of drug abuse so it is recommended to study the effect of other abused drugs on these hormones.

Association of the Human Leptin Receptor Gene (rs1137101; Gln223Arg) Polymorphism and Circulating Leptin in Patients with Metabolic Syndrome in the Indian Population.

Phenotypic expression of metabolic syndrome is precipitated by environmental variables along with the individual genetic susceptibility to the obesogenic environment and growing body of evidence suggest a paramount role of adipocytokines. Therefore, identifying the genetic influence on circulation leptin levels and clarifying genotype-phenotype correlation of rs1137101 {Leptin receptor gene (LEPR) Gln223Arg (Q223R; A668G)} in metabolic syndrome were the primary objective of this study. A total of 447 adult participants, including 214 metabolic syndrome patients and 233 healthy controls, were genotyped using polymerase chain reaction-restriction fragment length polymorphism method to unravel the effects of genetic risk loci {Leptin receptor gene; Gln223Arg (Q223R; A668G); rs1137101} on the occurrence of metabolic syndrome in consort with circulation leptin levels. Suitable descriptive statistics was used for different variables. The genotype frequencies were found to be in Hardy-Weinberg equilibrium for both cases (p > 0.2722) as well as in controls (p > 0.2331). However, genotype (x2: 11.26, 2 d.f. p = 0.0036) and allele distribution (x2: 10.51, 2 d.f. p: 0.0012) of the LEPR Gln223Arg (Q223R; A668G) differed significantly between cases and controls. Gln/Arg genotype (OR = 1.6099; 95% CI = 1.0847-2.3893; p value = 0.0181), Arg/Arg genotype (OR = 2.8121; 95% CI = 1.4103-5.6074; p value = 0.0033) and R allele (OR = 1.5875; 95% CI = 1.1996-2.1008; p value = 0.0012) were significantly associated with increased risk of metabolic syndrome in univariate analysis. Further a multivariate logistic regression adjusted for potential confounders showed that Arg/Arg genotype (OR = 1.9; 95% CI = 1.271-2.639; p-value < 0.05) and Gln/Arg (OR: 1.3; 95% CI = 0.873-2.034; p value < 0.05) have a significant risk for the occurrence of the metabolic syndrome. A progressive increase in the serum leptin levels from major homozygous alleles to minor homozygous alleles were observed indicating that rs1137101 modify the serum leptin concentrations in patients with metabolic syndrome. These findings provide enough evidence of a significant association of LEPR Gln223Arg (Q223R; A668G) polymorphism in the LepR gene in Indian patients with increased risk of metabolic syndrome for R allele and Arg/Arg homozygote. Thus, rs1137101 might be a pleiotropic locus for metabolic syndrome and its components in studied population.

Tetraploid genes of leptin (leptin-AI, -AII, -BI and -BII) in goldfish: Molecular cloning, bioinformatics analysis, tissue distribution and differential regulation of transcript expression by glucocorticoids

In mammals, leptin is an endocrine hormone involved in the regulation of feeding and energy metabolism, and glucocorticoids were previously reported to induce leptin gene expression. However, the link between glucocorticoids and leptin in fish has not been investigated. Goldfish are tetraploid teleosts because of genomic replication events (FSGD or 3-R), and some specific genes have quadrupled. In this study, two goldfish leptin-B genes, namely, leptin-BI (GenBank: ON468243) and leptin-BII (GenBank: ON468244), were cloned. The cDNA sequences of leptin-AI (GenBank: FJ534535.1) and leptin-AII (GenBank: FJ854572.1) have been reported by our team previously. Goldfish leptin-AI, -AII, -BI and -BII genes are located on chromosomes 43, 18, 29 and 4, respectively. In goldfish, leptin-B proteins shared approximately 30 % amino acid identities with leptin-A proteins and only 20 % with human leptin; however, either goldfish leptin-A or leptin-B showed high amino acid homology between themselves, 79.29 % and 82.74 %, respectively. The four leptin genes in goldfish are all highly conserved in three-dimensional (3-D) protein structures and gene structures. A tissue expression study showed that both the A and B forms of goldfish leptins are predominantly in the brain and liver. The effects of glucocorticoids on four leptin transcripts expression in goldfish were investigated by in vivo intraperitoneal injection and in vitro cell incubation approaches. The results showed that cortisol inhibited hepatic leptin-A transcript expression in a dose-dependent manner, while cortisol stimulated hepatic leptin-B mRNA expression, and RU486 (glucocorticoid receptor inhibitor) abolished cortisol’s effect on hepatic leptin-A and leptin-B mRNA expression. These results reflected the differential regulation of leptin-A and leptin-B by glucocorticoids in goldfish, which implied that leptin-A and leptin-B may mediate different functions in goldfish.

Transcriptome Analysis of Turbot (Scophthalmus maximus) Infected With Aeromonas salmonicida Reveals a Direct Effect on Leptin Synthesis as a Neuroendocrine Mediator of Inflammation and Metabolism Regulation

Aeromonas salmonicida subsp. salmonicida is the causative agent of furunculosis, a disease affecting numerous fish species worldwide. It is a highly pathogenic bacterium for turbot, whose farming production represents an important economic activity in several European countries and China. To better understand the response of this organism to A. salmonicida, we conducted RNA-Seq analysis of the head kidney from experimentally infected and uninfected turbot juveniles at 24 hours post-infection (hpi). As expected, among the differentially expressed genes (DEGs) between infected and uninfected fish, we observed the modulation of a multitude of immune-related genes but also a high representation of genes linked to metabolism. Interestingly, one of the most upregulated genes was that encoding the hormone leptin. Leptin is a multifunctional hormone/cytokine that has been shown to play roles in the immune system, stress response, food intake, metabolism and energy balance. We used recombinant human leptin to elucidate its role during infection with A. salmonicida in turbot (anorexigenic activity, ability to modulate metabolism and the immune response, and its effect on survival and bacterial load during infection). We found that the intraperitoneal administration of leptin was able to alter the response to the bacteria at the immune level, but especially at the metabolic level, which resulted in a higher survival rate without affecting the bacterial load. Based on this, we hypothesized that leptin could offer great potential as a therapeutic treatment during furunculosis outbreaks by reducing the impact of sepsis. Our results reveal the complex interplay between bacterial activity and the regulation of food intake, metabolism and inflammation.

Exogenous leptin enhances markers of airway fibrosis in a mouse model of chronic allergic airways disease

BackgroundAsthma patients with comorbid obesity exhibit increased disease severity, in part, due to airway remodeling, which is also observed in mouse models of asthma and obesity. A mediator of remodeling that is increased in obesity is leptin. We hypothesized that in a mouse model of allergic airways disease, mice receiving exogenous leptin would display increased airway inflammation and fibrosis.MethodsFive-week-old male and female C57BL/6J mice were challenged with intranasal house dust mite (HDM) allergen or saline 5 days per week for 6 weeks (n = 6–9 per sex, per group). Following each HDM exposure, mice received subcutaneous recombinant human leptin or saline. At 48 h after the final HDM challenge, lung mechanics were evaluated and the mice were sacrificed. Bronchoalveolar lavage was performed and differential cell counts were determined. Lung tissue was stained with Masson’s trichrome, periodic acid-Schiff, and hematoxylin and eosin stains. Mouse lung fibroblasts were cultured, and whole lung mRNA was isolated.ResultsLeptin did not affect mouse body weight, but HDM+leptin increased baseline blood glucose. In mixed-sex groups, leptin increased mouse lung fibroblast invasiveness and increased lung Col1a1 mRNA expression. Total lung resistance and tissue damping were increased with HDM+leptin treatment, but not leptin or HDM alone. Female mice exhibited enhanced airway responsiveness to methacholine with HDM+leptin treatment, while leptin alone decreased total respiratory system resistance in male mice.ConclusionsIn HDM-induced allergic airways disease, administration of exogenous leptin to mice enhanced lung resistance and increased markers of fibrosis, with differing effects between males and females.

Early onset obesity due to a mutation in the human leptin receptor gene.

SummaryLeptin is secreted by adipocytes in response to fat storage and binds to its receptor (LEPR), which is ubiquitously expressed throughout the body. Leptin regulates energy expenditure and is anorexigenic. In this study, we describe the clinical and hormonal findings of three siblings with a personal history of rapid weight gain during the first months of life. They had delayed puberty, high levels of FSH (15.6 ± 3.7 mUI/mL; reference: 1.5–12.4) and LH (12.3 ± 2.2 mUI/mL; reference: 1.7–8.6), normal oestradiol and total testosterone and successful fertility. None of the patients had dyslipidemia, diabetes or thyroid disease. Next-generation sequencing identified a pathogenic homozygous variant c.2357T>C, p.(Leu786Pro) in LEPR. Their parents and children were heterozygous for this mutation. We compared clinical and biochemical findings of homozygous carriers with first-degree heterozygous family members and ten randomly selected patients with adult-onset morbid obesity. Homozygous carriers of the mutation had significantly higher BMI (32.2 ± 1.7 kg/m2 vs 44.5 ± 7.1 kg/m2, P = 0.023) and increased serum levels of leptin (26.3 ± 9.3 ng/mL vs 80 ± 36.4 ng/mL, P = 0.028) than their heterozygous relatives. Compared with the ten patients with adult-onset morbid obesity, serum levels of leptin were not significantly higher in homozygous carriers (53.8 ± 24.1 ng/mL vs 80 ± 36.4 ng/mL, P = 0.149), and thus serum levels of leptin were not a useful discriminative marker of LEPR mutations. We described a rare three-generation family with monogenic obesity due to a mutation in LEPR. Patients with early onset obesity should be considered for genetic screening, as the identification of mutations may allow personalized treatment options (e.g. MC4R-agonists) and targeted successful weight loss.Learning pointsThe early diagnosis of monogenic forms of obesity can be of great interest since new treatments for these conditions are becoming available.Since BMI and leptin levels in patients with leptin receptor mutations are not significantly different from those found in randomly selected morbid obese patients, a careful medical history is mandatory to suspect this condition.Loss of leptin receptor function has been associated with infertility. However, our patients were able to conceive, emphasizing the need for genetic counselling in affected patients with this condition.

Leptin induces leiomyoma cell proliferation and extracellular matrix deposition via JAK2/STAT3 and MAPK/ERK pathways

To investigate the molecular effects of leptin on uterine leiomyoma cells. Experimental study using invitro culture of immortalized human leiomyoma (HuLM) cells. Academic university center. Women with uterine fibroids who underwent a hysterectomy or myomectomy. Administration of human recombinant leptin to the media of cultured HuLM cells separately or in combination with pharmacologic Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) or mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) inhibitors. We examined HuLM tissues and cells for the expression of the leptin receptor, termed OB-R. Cellular proliferation was measured at 6, 24, and 48 hours using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. Protein expression levels of proliferating cell nuclear antigen, collagen 1, phosphorylated STAT3/total STAT3, and phosphorylated ERK1/2 and total ERK1/2 were quantified using immunoblotting. Pharmacologic inhibitors were employed to further assess the role of the JAK2/STAT3 and MAPK/ERK pathways in the proliferative response. The presence of OB-R was confirmed in clinical leiomyoma and myometrial tissue obtained from 3 separate human subjects using immunofluorescence staining, and the expression of OB-R in HuLM cells was identified using immunoblotting. There was no significant difference in the expression of the leptin receptor in the myometrium compared with that in the leiomyoma tissue. Leptin stimulated cell proliferation and extracellular matrix (ECM) deposition at 24 hours after treatment. Pretreatment with a JAK2/STAT3 inhibitor attenuated ECM deposition, and pretreatment with a MAPK/ERK inhibitor significantly decreased leptin's stimulatory effect on cell proliferation and ECM deposition. Leptin induces a proliferative response and ECM deposition in HuLM cells. These findings suggest that leptin, acting through the JAK2/STAT3 and MAPK/ERK pathways, is involved in the development of uterine leiomyomas, which may partly explain their increased incidence in obese women.

Treatment Options for Lipodystrophy in Children.

Lipodystrophy includes a heterogeneous group of rare diseases characterized by different amounts of adipose tissue loss and several metabolic complications, including hypertriglyceridemia, steatohepatitis and particularly insulin resistance, that may lead to severe morbidity and, sometimes, mortality. Therefore, therapy for lipodystrophy primarily consists of a conventional approach that involves standard treatments of metabolic abnormalities. Given the evidence of leptin deficiency in lipodystrophy syndromes, leptin replacement therapy has been considered as a treatment option. Long-term studies on the use of therapy with a methionylated analog of human leptin, metreleptin, first on animals and subsequently on human patients, demonstrated enormous improvements of patients’ clinical features and metabolic conditions. Recently, metreleptin was approved by Food and Drug Administration (FDA) for the treatment of generalized lipodystrophy and by European Medicines Agency (EMA) for the treatment of both generalized and partial lipodystrophy. However, further research is being conducted for new and different therapeutic agents, especially helpful for the treatment of patients with partial lipodystrophy, as some of them do not have access to metreleptin therapy or show poor response.

The effect of omentectomy on the blood levels of adipokines in obese patients with endometrial cancer

ObjectiveTo investigate the blood levels of adipokines in obese patients with endometrial cancer who have and have not undergone omentectomy. MethodsBetween September 2017 and September 2019, the study recruited 54 patients with endometrial cancer. Measurements were taken of blood levels of human leptin, perilipin-1, adiponectin, adipolin, resistin, visfatin, and estrone preoperatively and postoperatively before adjuvant therapy or at the end of one month. The serum samples were separated by centrifugation for 10 mins at 3,000 revolutions/min, then stored at −80 °C until assay. ResultsIn this prospective study, a total of 54 endometrial cancer patients were analyzed in two separate groups according to the omentectomy status. Comprehensive staging surgery with omentectomy and without omentectomy was performed in 26 patients and 28 patients, respectively. The age, body mass index, body fat index, waist circumference, and skin thickness values of the patients with and without omentectomy were found to be similar. No statistically significant difference was determined between the patients with and without omentectomy in respect of the blood level of the adipokines measured preoperatively. A strong statistically significant correlation was determined between the pre and postoperative levels of Human Leptin (p = 0.002), perilipin-1(p = 0.001), adipolin (p < 0.001), adiponectin (p < 0.001), resistin (p = 0.001), visfatin (p < 0.001), and estrone (p = 0.004) (r = −0.43, −0.47, 0.75, 0.84, −0.47, - 0.58, −0.41, respectively) ConclusionsOmentectomy affected the postoperative blood levels of adipokines in obese patients with endometrial cancer. As omentectomy may have some positive effects on metabolism in these patients, it may be considered during endometrial cancer surgery due to the possible positive metabolic effects.

-2548G>A LEP Polymorphism Is Positively Associated with Increased Leptin and Glucose Levels in Obese Saudi Patients Irrespective of Blood Pressure Status

Background and Objectives: In this study, we aimed to investigate the link between common -2548G>A (rs7799039) promoter variant of the human leptin gene (LEP) with leptin and serum glucose leptin levels in obese Saudi patients. Materials and Methods: A total of 206 Saudi adults (80 obese normotensive nondiabetics, 76 obese hypertensive with Type 2 Diabetes and 50 normotensive nondiabetic controls) were genotyped for -2548G>A LEP polymorphism using the polymerase chain reaction-restriction fragment-length polymorphism technique. Results: Participants with minor AA genotype had significantly higher blood glucose levels (6.8 ± 0.55 mmol/L vs. 5.8 ± 0.30 mmol/L; p < 0.04) and HOMA-IR (4.1 ± 0.84 vs. 2.6 ± 0.67; p = 0.03) against those carrying major GG genotype. Participants with heterozygous GA genotype had significantly higher serum leptin levels against those carrying major GG genotype (40.0 ± 2.6 ng/mL vs. 29.6 ± 2.6 ng/mL; p = 0.04). Further investigation showed that individuals with AA, GA, GA + AA genotypes are at greater risk of developing hyperglycemia compared to those with GG genotype [OR 3.7(1.6–8.4), p = 0.001; 3.2 (1.2–8.6), p = 0.03; 3.5 (1.6–7.7), p = 0.001, respectively]. Additionally, the -2548AA allele was shown to be a risk factor for hyperglycemia [OR 1.9 (1.2–3.0), p = 0.006]. Our data revealed no relationship between this variant of the LEP gene with systolic and diastolic BP, signifying that this genetic variant is not a significant marker of obesity and hypertension in the Saudi population. Conclusions: AA and GA genotypes and LEP gene -2548AA alleles may signify potent risk factors predisposing healthy individuals to develop T2DM regardless of blood-pressure profile.

Atomistic mechanism of leptin and leptin-receptor association

The leptin-leptin receptor complex is at the very core of energy homeostasis and immune system regulation, among many other functions. In this work, we built homology models of leptin and the leptin binding domain (LBD) of the receptor from humans and mice. Docking analyses were used to obtain the coordinates of the native leptin-LBD complexes and a mixed heterodimer formed by human leptin and mouse LBD. Molecular dynamics (MD) simulations were performed using all models (monomers and heterodimers) as initial coordinates and the GROMACS program. The overall structural and dynamical behaviors are similar for the three complexes. Upon MD simulations, several new interactions appear. In particular, hydrophobic interactions, with more than 90% persistence, seem to be the most relevant for the stability of the dimers, as well as the pair formed by Asp85Lep and Arg468LBD. This in silico analysis provides structural and dynamical information, at the atomistic level, about the mechanism of leptin-LBD complex formation and leptin receptor activation. This knowledge might be used in the rational drug design of therapeutics to modulate leptin signaling. Communicated by Ramaswamy H. Sarma

The evolving epidemiology and differential etiopathogenesis of eating disorders: implications for prevention and treatment.

The evolving epidemiology and differential etiopathogenesis of eating disorders: implications for prevention and treatment.

Association of Leptin Receptor Q223R Gene Polymorphism and Breast Cancer Patients: A Case Control Study.

Introduction:Leptin is a hormone secreted from adipocytes that regulates metabolism and energy homeostasis through the leptin receptor (LEPR). The aim of this study was to investigate the association of leptin receptor gene Q223R gene polymorphism, and plasma leptin level among obese breast cancer females. Materials and Methods:The study enrolled 160 breast cancer patients and 160 healthy control females. LEPR Q223R polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum leptin was determined using enzyme-linked immunosorbent assay human leptin kit. Immunohistochemical tests from paraffin blocks were carried out for estrogen and progesterone staging using the precise antibodies. Results:An association was found between LEPR gene Q223R gene polymorphism among obese breast cancer females. Statistical difference was found between GG (60.6%) Arg/Arg genotype (OR=2.986; 95%CI=1.540 to 5.789; p= 0.001) compared to AA (33.1%) Gln/Gln genotype. GG Q223R LEPR polymorphism showed statistically significant difference among obese breast cancer patients (BMI more than 25) compared to control (P < 0.0001). GG genotype of Q223R LEPR polymorphism showed statistically significant increased leptin level (p-value =0.0001) among obese patients (mean± SD; 23.39±4.32) compared to control (17.83±5.67). Conclusions:Q223R LEPR polymorphism GG genotype was associated with increased leptin profile among obese breast cancer females.

Body-fat sensor triggers ribosome maturation in the steroidogenic gland to initiate sexual maturation in Drosophila.

Fat stores are critical for reproductive success and may govern maturation initiation. Here, we report that signaling and sensing fat sufficiency for sexual maturation commitment requires the lipid carrier apolipophorin in fat cells and Sema1a in the neuroendocrine prothoracic gland (PG). Larvae lacking apolpp or Sema1a fail to initiate maturation despite accruing sufficient fat stores, and they continue gaining weight until death. Mechanistically, sensing peripheral body-fat levels via the apolipophorin/Sema1a axis regulates endocytosis, endoplasmic reticulum remodeling, and ribosomal maturation for the acquisition of the PG cells' high biosynthetic and secretory capacity. Downstream of apolipophorin/Sema1a, leptin-like upd2 triggers the cessation of feeding and initiates sexual maturation. Human Leptin in the insect PG substitutes for upd2, preventing obesity and triggering maturation downstream of Sema1a. These data show how peripheral fat levels regulate the control of the maturation decision-making process via remodeling of endomembranes and ribosomal biogenesis in gland cells.

Metreleptin treatment of non-HIV lipodystrophy syndromes

Lipodystrophy syndromes (LS) constitute a group of rare diseases of the adipose tissue, characterized by a complete or selective deficiency of the fat mass. These disorders are associated with important insulin resistance, cardiovascular and metabolic comorbidities that impact patient's survival and quality of life. Management is challenging and includes diet, physical activity, and specific pharmacological treatment of LS-associated comorbidities. Because of a common pathophysiology involving decreased concentration of the adipokine leptin, efforts have been made to develop therapeutic strategies with leptin replacement therapy. Metreleptin, a recombinant human leptin analogue, has been proposed in hypoleptinemic patients since the beginning of 2000’s. The treatment leads to an improvement in metabolic parameters, more important in generalized than in partial LS forms. In this review, the current knowledge about the development of the drug, its outcomes in the treatment of lipodystrophic patients as well as the peculiarities of its use will be presented.

Human Milk Glucose, Leptin, and Insulin Predict Cessation of Full Breastfeeding and Initiation of Formula Use.

Objective: We aimed to investigate prospective associations between milk bioactives related to metabolic health (glucose, insulin, leptin, C reactive protein [CRP], and interleukin 6 [IL-6]) and incident formula initiation at 3 and 6 months postpartum. Design: This study included 363 mother-infant dyads who were fully breastfed at 1 month and participated in the prospective Mothers and Infants Linked for Healthy Growth study from pregnancy to 6 months postpartum. Associations between milk glucose, leptin, insulin, CRP, and IL-6 at 1 and 3 months and incident formula feeding (FF) at 3 and 6 months, respectively, were tested using multiple logistic regression, adjusting for numerous potential confounders such as maternal age and prepregnancy body mass index. Results: At 3 months postpartum, 1-month glucose (odds ratio [OR] 0.45 [95% confidence interval (CI): 0.27-0.75], p ≤ 0.01) and smaller decreases in glucose from 1 to 3 months (OR 0.51 [95% CI: 0.28-0.92], p = 0.03) were associated with lower odds of FF, whereas 1-month leptin (OR 2.30 [95% CI: 1.30-4.07], p < 0.01) and larger increase in insulin (OR 1.86 [95% CI: 1.23-2.81], p < 0.01) and leptin (OR 2.17 [95% CI: 1.29-3.68], p < 0.01) from 1 to 3 months were associated with increased odds of FF. At 6 months, insulin increases (OR 2.08 [95% CI: 1.03-4.17], p = 0.04) were associated with higher odds of FF. Conclusions: In a cohort of women with established lactation, 1-month milk glucose, insulin, and leptin predicted initiation of FF at 3 months. Early milk composition may provide a window into mammary gland function, allowing identification of women at risk of not meeting their breastfeeding goals.

Association between Leptin and Adiponectin in women with Polycystic Ovary Syndrome in North Indian Population

Polycystic ovary syndrome (PCOS) is one of the most common endocrine abnormalities, characterized by biochemical hyperandrogenaemia, chronic anovulation, and polycystic ovaries. The objective of the present study to determine the association of adiponectin and leptin with women with PCOS in North Indian Women. In the hospital-based case-control study 100 women with PCOS and 100 controls were recuited from RAMA Medical College, Kanpur, India. Five ml venous blood sample was collected under aseptic precaution and transferred in the serum separator tubes. Leptin and adiponectin levels were assayed by human sensitive leptin double-antibody sandwich enzyme-linked immunosorbent one-step process assay (QAYEE-BIO life science) according to instructions provided with the kit. In the multivariable logistic regression analysis, leptin was found to be independently associated with 1.14 times higher risk for PCOS (OR 1.14, 95% CI 1.01 to 1.29). Receiver operating curve (ROC) analysis suggested excellent predictive accuracy of the multivariable model with Area under the curve 0.86. In the ROC analysis leptin was associated with 68% area under the curve for predicting PCOS using cut off value of &gt;7.87, (P&lt;0.001, Sensitivity 87.8, Specificity 49.4). Adiponectin level was not significantly associated with predicting PCOS (Area under the curve 0.54, P =0.30, Sensitivity 71.1, specificity 50.5, cut off value &lt;10.2). To conclude we observed that higher leptin levels were independently associated with the risk of PCOS, however adiponectin level was not independently associated with the risk of PCOS.

Potential sex differences in human milk leptin and their association with asthma and wheeze phenotypes: Results of the Ulm Birth Cohorts.

The hormone leptin has been suggested to play a role in the respiratory and immune systems. Evidence on sex-specific concentrations of leptin in human milk and sex-specific associations with the development of asthma and wheeze has been put forward but is still scarce. To investigate whether male and female infants receive different levels of leptin through human milk and whether leptin is implicated in the development of asthma and wheeze in a sex-dependent manner using data from the two Ulm Birth Cohort studies. Leptin data were available from human milk samples collected at 6weeks (Ulm Birth Cohort Study [UBCS, n=678; Ulm SPATZ Health Study, n=587]), and, in SPATZ only, at 6months (n=377) and 12months (n=66) of lactation. Sex-specific associations with doctor-diagnosed asthma and wheeze phenotypes were assessed in crude and adjusted models using logistic regression. Adjustments were made for maternal allergy, exclusive breastfeeding, infant age at the time of milk sampling, and child BMI z-score. At 6weeks, leptin levels (median [min, max], in ng/L) were higher in the milk for girls (197 [0.100, 4120]) than in milk for boys (159 [1.02, 3280], p=.045) in UBCS. No significant sex differences were observed in SPATZ (p=.152). There were no significant associations of leptin with asthma or wheeze in both studies, even in a sex-dependent manner (p>.05). It remains unclear whether male and female infants receive different levels of leptin through human milk. However, leptin in human milk may not be associated with history and development of asthma and wheeze in a sex-specific manner.