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BackgroundWeight and waist gain are significant concerns in adulthood. Both weight and waist gain are particularly important among South Asians, known to have an increased risk of developing chronic cardiometabolic complications at any body mass index compared to other racial and ethnic groups. The aim of this study was to investigate factors predicting weight and waist gain in a longitudinal cohort of South Asians living in the US (United States).MethodsThis was a prospective analysis using data from exam 1 (2010-2013) and exam 2 (2015-2018) of the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study, a prospective cohort study of South Asians (recruited from San Francisco and Chicago), with a mean 4.8 years of follow-up.ResultsOf 634 participants studied (42.7 % women, mean age 55 years, BMI 25.7 kg/m2, weight 70.4 kg at exam 1), 34.7 % had gained ≥5 % weight and 32.3 % gained ≥5 % waist at exam 2. In the adjusted models, older age, higher number of years of US residence, and having diabetes were associated with lower odds of weight gain; being female and having higher adiponectin were associated with higher odds of weight gain. Being female and being employed full/part time or being retired predicted lower likelihood of waist gain. Being single, separated/divorced, having a higher leptin and a higher C-reactive protein level predicted higher likelihood of waist gain.ConclusionsThe current study identified several social, demographic, and clinical factors that can serve as targets for obesity interventions among US South Asians. In addition, this study also raises hypotheses about associations of adipokine levels with weight and waist gain.

Timed feeding drives adipose browning, although the integrative mechanisms for the same remain unclear. Here, we show that twice-a-night (TAN) feeding generates biphasic oscillations of circulating insulin and leptin, representing their entrainment by timed feeding. Insulin and leptin surges lead to marked cellular, functional, and metabolic remodeling of subcutaneous white adipose tissue (sWAT), resulting in increased energy expenditure. Single-cell RNA-sequencing (scRNA-seq) analyses and flow cytometry demonstrate a role for insulin and leptin surges in innate lymphoid type 2 (ILC2) cell recruitment and sWAT browning, since sWAT depot denervation or loss of leptin or insulin receptor signaling or ILC2 recruitment each dampens TAN feeding-induced sWAT remodeling and energy expenditure. Consistently, recreating insulin and leptin oscillations via once-a-day timed co-injections is sufficient to favorably remodel innervated sWAT. Innervation is necessary for sWAT remodeling, since denervation of sWAT, but not brown adipose tissue (BAT), blocks TAN-induced sWAT remodeling and resolution of inflammation. In sum, reorganization of nutrient-sensitive pathways remodels sWAT and drives the metabolic benefits of timed feeding.

Adipose tissues serve as an energy reservoir and endocrine organ, yet the mechanisms that coordinate these functions remain elusive. Here, we show that the transcriptional coregulators, YAP and TAZ, uncouple fat mass from leptin levels and regulate adipocyte plasticity to maintain metabolic homeostasis. Activating YAP/TAZ signalling in adipocytes by deletion of the upstream regulators Lats1 and Lats2 results in a profound reduction in fat mass by converting mature adipocytes into delipidated progenitor-like cells, but does not cause lipodystrophy-related metabolic dysfunction, due to a paradoxical increase in circulating leptin levels. Mechanistically, we demonstrate that YAP/TAZ-TEAD signalling upregulates leptin expression by directly binding to an upstream enhancer site of the leptin gene. We further show that YAP/TAZ activity is associated with, and functionally required for, leptin regulation during fasting and refeeding. These results suggest that adipocyte Hippo-YAP/TAZ signalling constitutes a nexus for coordinating adipose tissue lipid storage capacity and systemic energy balance through the regulation of adipocyte plasticity and leptin gene transcription.

Chronic use of nicotine is known to dysregulate metabolic signaling through altering circulating levels of feeding-related hormones, contributing to the onset of disorders like type 2 diabetes. However, little is known about the acute effects of nicotine on hormonal signaling. We previously identified an acute increase in food intake following acute nicotine, and we sought to determine whether this behavior was due to a change in hormone levels. We first identified that acute nicotine injection produces an increase in feeding behavior in dependent rats, but not nondependent rats. We confirmed that chronic nicotine use increases circulating levels of insulin, leptin, and ghrelin, and these correlate with rats' body weight and food intake. Acute nicotine injection in dependent animals decreased circulating GLP-1 and glucagon levels, and administration of glucagon prior to acute nicotine injection prevented the acute increase in feeding behavior. Thus, acute nicotine injection increases feeding behavior in dependent rats by decreasing glucagon signaling.

Epilepsy affects 65 million people globally and causes neurobehavioral, cognitive, and psychological defects. Although research on the disease is progressing and a wide range of treatments are available, approximately 30% of people have refractory epilepsy that cannot be managed with conventional medications. This underlines the importance of further understanding the condition and exploring cutting-edge targets for treatment. Adipokines are peptides secreted by adipocyte's white adipose tissue, involved in controlling food intake and metabolism. Their regulatory functions in the central nervous system (CNS) are multifaceted and identified in several physiology and pathologies. Adipokines play a role in oxidative stress and neuroinflammation which are associated with brain degeneration and connected neurological diseases. This review aims to highlight the potential impacts of leptin, adiponectin, apelin, vaspin, visfatin, and chimerin in the pathogenesis of epilepsy. [ABSTRACT FROM AUTHOR]

Objective: Treatment for anorexia nervosa (AN) remains challenging; there are no approved psychopharmacological interventions and psychotherapeutic strategies have variable efficacy. The investigation of evidence‐based treatments has so far been compounded by an underdeveloped understanding into the neurobiological changes associated with the acute stages of AN. There is converging evidence of deficiencies in neuroplasticity in AN. Method: This paper provides an overview of neuroimaging, neuropsychological, molecular and qualitative findings relating to neuroplasticity in AN, translating these findings to the identification of novel biological and psychotherapeutic strategies. Results: Novel psychopharmacological approaches that may ameliorate deficiencies in neuroplasticity include medications such as ketamine, psilocybin and human recombinant leptin. Anti‐inflammatory medications and brain‐derived neurotrophic factor mimetics may emerge as potential treatments following further research. Psychotherapeutic strategies that may target neuroplastic deficiencies, as well as having wider effects on identity, include imagery rescripting, memory specificity training, cognitive remediation therapy, exposure therapies, narrative therapies, cultural interventions (e.g. music and arts therapies) and yoga/mindfulness‐based interventions. Conclusions: Treatments specifically targeted towards mitigating the neurobiological sequalae of AN are warranted, and emerging neurobiological and neuropsychological research utilising longitudinal designs and large sample sizes, as well as initial feasibility studies, are necessitated to bolster translational efforts. Highlights: There is converging evidence from neuroimaging, neuropsychological, molecular and qualitative research suggestive of altered neuroplasticity during the acute stages of anorexia nervosa (AN), which is also a transdiagnostic feature across psychiatric disorders.Novel pharmacological treatments that are used for the treatment of other conditions in humans, and could be applied to target neuroplasticity in AN, include ketamine, psilocybin, human recombinant leptin and anti‐inflammatory medications.Psychotherapeutic strategies that may target neuroplastic deficiencies in AN, some of which have already been investigated, include those targeting cognitive problems or biases (e.g. imagery rescripting, memory specificity training, cognitive remediation therapy (CRT)), fear (e.g. exposure‐based therapies), stress (e.g. yoga/mindfulness‐based interventions) and identity (e.g. narrative therapies, cultural interventions such as arts and music‐based therapies). [ABSTRACT FROM AUTHOR]

• Proteome and phosphoproteome analyses were conducted on the olfactory bulb from depressed individuals. • Astrocyte markers were significantly enriched among the differentially abundant proteins. • RNA-fluorescence in situ hybridization revealed changes in the expression of key astrocytic genes. • The olfactory bulb proteome from socially defeated mice showed significant enrichment of oligodendrocyte markers. • These results highlight cerebral astrocytic dysfunction in depression. • These findings point to a critical difference in the olfactory bulb proteome of depressed 13 individuals and socially defeated mice. The olfactory bulb (OB), a major structure of the limbic system, has been understudied in human investigations of psychopathologies such as depression. To explore more directly the molecular features of the OB in depression, a global comparative proteome analysis was carried out with human post-mortem OB samples from 11 males having suffered from depression and 12 healthy controls. We identified 188 differentially abundant proteins (with adjusted p < 0.05) between depressed cases and controls. Gene ontology and gene enrichment analyses suggested that these proteins are involved in biological processes including the complement and coagulation cascades. Cell type enrichment analysis displayed a significant reduction in several canonical astrocytic proteins in OBs from depressed patients. Furthermore, using RNA-fluorescence in-situ hybridization, we observed a decrease in the percentage of ALDH1L1+ cells expressing canonical astrocytic markers including ALDOC , NFIA , GJA1 (connexin 43) and SLC1A3 (EAAT1). These results are consistent with previous reports of downregulated astrocytic marker expression in other brain regions in depressed patients. We also conducted a comparative phosphoproteomic analysis of OB samples and found a dysregulation of proteins involved in neuronal and astrocytic functions. To determine whether OB astrocytic abnormalities is specific to humans, we also performed proteomics on the OB of socially defeated male mice, a commonly used model of depression. Cell-type specific analysis revealed that in socially defeated animals, the most striking OB protein alterations were associated with oligodendrocyte-lineage cells rather than with astrocytes, highlighting an important species difference. Overall, this study further highlights cerebral astrocytic abnormalities as a consistent feature of depression in humans. [ABSTRACT FROM AUTHOR]

The neurons of the melanocortin system regulate feeding and energy homeostasis through a combination of electrical and endocrine mechanisms. However, the molecular basis for this functional heterogeneity is poorly understood. Here, a voltage‐gated potassium (Kv+) channel named KCNB1 (alias Kv2.1) forms stable complexes with the leptin receptor (LepR) in a subset of hypothalamic neurons including proopiomelanocortin (POMC) expressing neurons of the Arcuate nucleus (ARHPOMC). Mice lacking functional KCNB1 channels (NULL mice) have less adipose tissue and circulating leptin than WT animals and are insensitive to anorexic stimuli induced by leptin administration. NULL mice produce aberrant amounts of POMC at any developmental stage. Canonical LepR‐STAT3 signaling—which underlies POMC production—is impaired, whereas non‐canonical insulin receptor substrate PI3K/Akt/FOXO1 and ERK signaling are constitutively upregulated in NULL hypothalami. The levels of proto‐oncogene c‐Fos—that provides an indirect measure of neuronal activity—are higher in arcuate NULL neurons compared to WT and most importantly do not increase in the former upon leptin stimulation. Hence, a Kv channel provides a molecular link between neuronal excitability and endocrine function in hypothalamic neurons. [ABSTRACT FROM AUTHOR]

At the time of breast cancer diagnosis, most patients meet the diagnostic criteria to be classified as obese or overweight. This can significantly impact patient outcome: breast cancer patients with obesity (body mass index > 30) have a poorer prognosis compared to patients with a lean BMI. Obesity is associated with hyperleptinemia, and leptin is a well-established driver of metastasis in breast cancer. However, the effect of hyperleptinemia on angiogenesis in breast cancer is less well-known. Angiogenesis is an important process in breast cancer because it is essential for tumor growth beyond 1mm³ in size as well as cancer cell circulation and metastasis. This review investigates the role of leptin in regulating angiogenesis, specifically within the context of breast cancer and the associated tumor microenvironment in obese patients. [ABSTRACT FROM AUTHOR]

Background: Ketamine has emerged as a prominent substance of misuse. Leptin, an adipocyte-derived polypeptide hormone, has been implicated in the development of addiction. Sex-specific changes in leptin levels have been demonstrated following acute ketamine administration; the persistence of long-term ketamine use on leptin levels is uncertain.Objectives: To assess the sex-difference of leptin levels, and their persistence, in individuals with ketamine use disorder (KUD) compared to healthy controls.Methods: Plasma leptin levels were measured in 62 healthy controls (37 males, 25 females) and 68 participants with KUD (50 males, 18 females) on the first day (baseline) and after 1 and 2 weeks of abstinence. As leptin levels are affected by body mass index (BMI), BMI-adjusted leptin (leptin/BMI ratio) was also examined. Mixed model for repeated measures was used to examine changes after ketamine abstinence.Results: Compared to same-sex controls, female, but not male, participants with KUD demonstrated lower leptin levels and leptin/BMI ratio at baseline, week 1, and week 2 (leptin levels: p = .001, 0.006 and 0.032, respectively; leptin/BMI ratio: p = .004, 0.022, and 0.09, respectively). Repeated measures showed that leptin levels and the leptin/BMI ratio increased after 2 weeks of abstinence in male participants with KUD (p = .002 and 0.011, respectively), but females did not show such an increase (p > .05).Conclusions: Sex-specific differences were observed in leptin levels and the leptin/BMI ratio in individuals with KUD compared to controls. Lower leptin levels in females with KUD persisted after 2 weeks of abstinence. [ABSTRACT FROM AUTHOR]

Human milk comprehensively meets the nutritional needs of a child, providing not only structural and energy components but also various bioactive factors. Among these, neurotrophic factors and hormones involved in metabolic processes deserve special attention. Studies using enzyme-linked immunosorbent assays compared the content of neurotrophic factors—CNTF, NT-3, and NGF—and hormones, leptin and insulin, in two groups of breast milk samples: early lactation (1–3 months) and extended lactation (>6 months, up to 12 months). The results indicated changes in leptin and insulin levels as the lactation period extended. NGF, leptin, and insulin were present in milk samples from both study groups, with leptin and insulin levels being higher in the early lactation group. CNTF and NT-3 were not detected in any of the samples from either study group. The analyses confirmed that human milk from women who breastfeed for extended periods remains a source of biologically active components and macronutrients that support a child's development and health. [ABSTRACT FROM AUTHOR]

Background: Sinetrol® Xpur is a polyphenolic ingredient rich in citrus flavonoids that has shown weight loss effects in previous studies. The dose dependent nature, gut microbial actions of this product has not been explored previously, thus presented in this study. Methods: In this open label study, we evaluated the effect of Sinetrol® Xpur supplementation on healthy but overweight/obese adults (20–50 yrs) for 16 weeks. Participants (n = 20) were randomly allocated to a high dose group (HD, 1800 mg/day) or low dose group (LD, 900 mg/day) of the product for 16 weeks. Fat composition, gut microbial composition, were evaluated using MRI and 16S rDNA sequencing respectively at week 1 and 16. Results: We observed HDL, HbA1C, LDL and leptin improved significantly over 16 weeks, irrespective of the dosage. There was a trend for decrease in visceral adipose tissue (VAT), BMI over time and body weight displayed a trend for dose dependent decrease. Eubacterium xylanophilum, Ruminococcacea UCG-004 genus which increased in HD and LD respectively were negatively associated to VAT. Both doses increased butyrate producers such as Eubacterium ruminantium and Ruminococcaceae NK4A214 genus. Conclusions: Overall chronic supplementation of Sinetrol® Xpur, irrespective of their dose improved HDL, HbA1c, LDL and leptin and tended to decrease visceral adipose tissue via changes in gut microbiota. Trial registration number NCT03823196. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions Social anxiety disorder (SAD) is a common disorder characterized by excessive fear of scrutiny and embarrassment, leading to severe distress and avoidance behaviors or dysfunctions. SAD and other relevant diseases have been reported to be associated with a higher risk of aging‐related diseases, such as Alzheimer's disease, Parkinson's disease, and diabetes mellitus. Recently, epigenetic clock analysis, which measures biological aging based on comprehensive DNA methylation (DNAm) status, has been widely conducted. We conducted epigenetic clock analyses in patients with SAD and controls, examining various epigenetic age acceleration and DNAm‐based predictive values of aging‐related proteins (GrimAge components and GrimAge2 components), including leptin level.We used the publicly available DNAm dataset, GSE164056, which consists of 66 patients with SAD and 77 controls of Caucasian descent aged between 18 and 50 years. We conducted regression analyses investigating the association between SAD and various indices of epigenetic aging, using age and sex as covariates.None of the epigenetic clocks showed significant differences in age acceleration. Of the DNAm‐based predictive values of aging‐related proteins, leptin level in GrimAge components (q = 0.0123) and GrimAge2 components (q = 0.0123) were significantly lower in patients with SAD than in controls.The results of this study suggested that leptin may be involved in SAD pathogenesis as an aging‐related protein. Therefore, further studies with different designs are required. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Overweight is associated with low‐grade systemic inflammation. However, its effect on neuroinflammation remains unclear. We examined the possible association between overweight and neuroinflammation using cerebrospinal fluid (CSF) in a nonclinical adult population in Japan.CSF and plasma levels of interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), plasma levels of C‐reactive protein (CRP), and leptin were measured in nonclinical adult participants (35 males and 34 females) who had no current or past history of neuropsychiatric diseases. We performed partial correlation analyses with sex and age as covariates between the body mass index (BMI) and the inflammatory markers and compared them between overweight and nonoverweight participants.The BMI significantly correlated with CSF levels of IL‐6 (rs = 0.32, p = 0.009), plasma levels of CRP (rs = 0.30, p = 0.016), IL‐1β (rs = 0.29, p = 0.019), IL‐6 (rs = 0.25, p = 0.042), TNF‐α (rs = 0.43, p < 0.001), and leptin (rs = 0.72, p < 0.001). Overweight participants (BMI ≧ 25) had significantly higher CSF levels of IL‐6 (p < 0.001), plasma levels of IL‐1β (p = 0.023), TNF‐α (p < 0.001), and leptin (p < 0.001) than the nonoverweight participants.Overweight is associated with central IL‐6, a marker for neuroinflammation, as well as systemic inflammation markers, even in a nonclinical population. [ABSTRACT FROM AUTHOR]

Background: Telomere length (TL), mitochondrial DNA copy number (mtDNAcn), and DNA methylation age (DNAmAge) are common aging biomarkers. However, research on the associations between these three markers at birth and subsequent metabolic status was limited. This study aimed to evaluate the association between TL, mtDNAcn, and DNAmAge in newborns and the variation in metabolic hormones of children at 3 years old. Methods: This research involved 895 mother–child pairs from a birth cohort in China, with TL and mtDNAcn measured using quantitative real-time PCR, DNA methylation (DNAm) assessed using Infinium MethylationEPIC Beadchip, and DNAm age (DNAmAge) determined using Horvath's epigenetic clock. Insulin and leptin levels were measured via electrochemiluminescence assay. Multivariable adjusted linear regression and restricted cubic spline (RCS) analysis were utilized to examine the association between aging markers and metabolic hormones. Results: The linear regression analysis indicated the percentage change of metabolism hormones for per doubling of aging biomarkers alterations and found significant associations between DNAmAge and insulin levels (adjusted percent change (95% CI), − 13.22 (− 23.21 to − 1.94)), TL and leptin levels (adjusted percent change (95% CI), 15.32 (1.32 to 31.24)), and mtDNAcn and leptin levels (adjusted percent change (95% CI), − 14.13 (− 21.59 to − 5.95)). The RCS analysis revealed significant non-linear associations between TL (Ln transformed) and insulin (Ln transformed) (P = 0.024 for nonlinearity), as well as DNAmAge (Ln transformed) and leptin (Ln transformed) (P = 0.043 for nonlinearity). Specifically, for TL and insulin, a positive association was observed when TL (Ln transformed) was less than − 0.05, which transitioned to an inverse association when TL (Ln transformed) was greater than − 0.05. Regarding DNAmAge and leptin, there was a sharp decline when DNAmAge (Ln transformed) was less than − 1.35, followed by a plateau between − 1.35 and − 0.67 and then a further decline when DNAmAge (Ln transformed) was greater than − 0.67. Conclusions: In this prospective birth cohort study, variation in metabolic hormones of children at 3 years old was associated with TL, mtDNAcn, and DNAmAge at birth. These findings suggested that TL, mtDNAcn, and DNAmAge might play a role in the biological programming of metabolic health from birth. [ABSTRACT FROM AUTHOR]

Chronic gastritis (CG) is a common inflammatory disease of chronic inflammatory lesion of gastric mucosa and in the diagnosis of gastritis in traditional Chinese medicine (TCM), CG can be classified into Cold ZHENG (syndrome in TCM) and Hot ZHENG. However, the molecular features of Cold/Hot ZHENG in CG and the mechanism of Cold/Hot herbs in formulae for CG remained unclear. In this study, we collected a transcriptomics data including 35 patients of Cold/Hot ZHENG CG and 3 scRNA-seq CG samples. And 25 formulae for CG and 89 herbs recorded in these formulae were also collected. We conduct a comprehensive analysis based on the combination of transcriptomics datasets and machine learning algorithms, to discover biomarkers for Cold/Hot ZHENG CG. Then the target profiles of the collected formulae and Cold/Hot herbs were predicted to uncover the features and biomarkers of them against Cold/Hot ZHENG CG. These biomarkers suggest that Hot ZHENG CG might be characterized by over-inflammation and exuberant metabolism, and Cold ZHENG CG showed a trend of suppression in immune regulation and energy metabolism. Biomarkers and specific pathways of Hot herbs tend to regulate immune responses and energy metabolism, while those of Cold herbs are more likely to participate in anti-inflammatory effects. Finally, the findings were verified based on public transcriptomics datasets, as well as transcriptomics and ELISA detection, taking Jin Hong tablets as a case study. Biomarkers like leptin and IL-6 together with proportions of immune cells showed significant changes after the intervention. These findings might reflect the mechanism and build a bridge between macro and micro views of Cold/Hot ZHENG as well as Cold/Hot herbs. [ABSTRACT FROM AUTHOR]

Objective: To explore the role and regulation mechanism of leptin in senescence of mouse cardiomyocytes (MCM). Methods: The mRNA expression levels of senescence related indicators p16, p21, and senescence ⁃ associated secretory phenotype (SASP)in leptin stimulated MCM were examined by qPCR; the protein expressions of p16, p21, γ⁃H2AX, PI3K, AKT, p⁃PI3K, and p⁃AKT were detected by Western blot; the senescence of MCM was detected by β⁃galactosidase staining. PI3K inhibitor (LY294002) was pretreated for 2 h and then stimulated with leptin, the mRNA and protein levels of p16 and p21 were detected by qPCR and Western blot; the mRNA levels of SASP were examined by qPCR; MCM senescence was detected by β⁃galactosidase staining. Results: In MCM stimulated by leptin, the mRNA and protein levels of p16 and p21, as well as the protein level of γ⁃H2AX increased, the mRNA levels of SASP［ (interleukin, IL)⁃1β, tumor necrosis factor (TNF)⁃α、IL⁃6, monocyte chemoattractant protein (MCP)⁃1］were up ⁃regulated, the phosphorylation levels of proteins in PI3K/AKT signaling pathway increased; and β⁃galactosidase staining showed the senescence of MCM. When pretreated with PI3K inhibitor for 2 h, the mRNA and protein levels of p16 and p21, as well as the protein level of γ ⁃ H2AX were down ⁃ regulated, and the expressions of SASP mRNA were down ⁃ regulated, the senescence of MCM was alleviated. Conclusion: Leptin regulates the progression of MCM senescence by activating PI3K/AKT signaling pathway and promoting SASP (IL⁃1β, TNF⁃α, IL⁃6 and MCP⁃1)secretion. [ABSTRACT FROM AUTHOR]

The primary objective of this study was to evaluate the effects of liquid (Fructose-added lactic acid bacteria, F-LAB) and commercial (Commercial LAB, C-LAB) probiotics sourced from Rye-Grass Lactic Acid Bacteria (LAB) on broiler chickens experiencing heat stress (HS). The research involved 240 broiler chicks, divided into six groups: control, F-LAB, C-LAB (raised at 24 °C), HS, F-LAB/HS, and C-LAB/HS (exposed to 5–7 h of 34–36 °C daily). The study followed a randomized complete block design, with each group consisting of 40 chicks. F-LAB and HS/F-LAB groups received a natural probiotic added to their drinking water at a rate of 0.5 ml/L, while C-LAB and HS/C-LAB groups were supplemented with a commercial probiotic at the same dosage. Control and HS groups received no probiotic supplementation. The duration of the study was 42 days, with data collected on growth performance, feed intake, feed conversion ratio, and health parameters. Statistical analyses were performed using ANOVA, and significant differences between groups were determined using post hoc tests. The results revealed that without probiotic supplementation, heat stress led to a decrease in body weight gain, T3 levels, citrulline, and growth hormone levels, along with an increase in the feed conversion ratio, serum corticosterone, HSP70, ALT, AST, and leptin levels (p < 0.05 for all). Heat stress also adversely affected cecal microbiota, reducing lactic acid bacteria count (LABC) while increasing Escherichia coli and coliform bacteria (CBC) counts. However, in the groups receiving probiotic supplementation under heat stress (F-LAB/HS and C-LAB/HS), these effects were alleviated (p < 0.05 for all). Particularly noteworthy was the observation that broiler chickens supplemented with natural lactic acid bacteria (F-LAB) exhibited greater resilience to heat stress compared to those receiving the commercial probiotic, as evidenced by improvements in growth, liver function, hormonal balance, intestinal health, and cecal microbiome ecology (p < 0.05). These findings suggest that the supplementation of naturally sourced probiotics (F-LAB) may positively impact the intestinal health of broiler chickens exposed to heat stress, potentially supporting growth and health parameters. [ABSTRACT FROM AUTHOR]

Purpose: Despite the introduction of Relative Energy Deficiency in Sport (RED-s) in 2014, there is evidence to suggest that male endurance athletes still present with a high prevalence of low energy availability (LEA). Previous findings suggest that energy availability (EA) status is strongly correlated with impairments in endocrine function such as reduced leptin, triiodothyronine (T3), and insulin, and elevated bone loss. This study aimed to report the current EA status, endocrine function and bone health of highly trained Irish male endurance athletes. Methods: In this cross-sectional study, participants (n = 3 triathletes; n = 10 runners) completed a 7-day testing period during the competition season using lab-based measures, to ascertain EA status, hormone level and rates of bone metabolism. Serum blood samples were obtained to assess hormone levels and markers of bone metabolism. Results: Mean EA was < 30 kcal/kg lean body mass (LBM)/day in 76.9% of athletes. There was a strong association between LEA and low carbohydrate intake, and lower LBM. Mean levels of insulin, IGF-1 and leptin were significantly lower than their reference ranges. Elevated mean concentrations of β-CTX and a mean P1NP: β-CTX ratio < 100, indicated a state of bone resorption. Conclusion: The EA level, carbohydrate intake, hormone status and bone metabolism status of highly trained male endurance athletes are a concern. Based on the findings of this study, more frequent assessment of EA across a season is recommended to monitor the status of male endurance athletes, in conjunction with nutritional education specific to EA and the associated risks. [ABSTRACT FROM AUTHOR]

In parallel to the legalization of cannabis for both medicinal and recreational purposes, cannabinoid use has steadily increased over the last decade in the United States. Cannabinoids, such as tetrahydrocannabinol and anandamide, bind to the central cannabinoid‐1 (CB1) receptor to impact several physiological processes relevant for body weight regulation, including appetite and energy expenditure. The hypothalamus integrates peripheral signals related to energy balance, houses several nuclei that orchestrate eating, and expresses the CB1 receptor. Herein we review literature to date concerning cannabinergic action in the hypothalamus with a specific focus on eating behaviors. We highlight hypothalamic areas wherein researchers have focused their attention, including the lateral, arcuate, paraventricular, and ventromedial hypothalamic nuclei, and interactions with the hormone leptin. This review serves as a comprehensive analysis of what is known about cannabinoid signaling in the hypothalamus, highlights gaps in the literature, and suggests future directions. [ABSTRACT FROM AUTHOR]

Simple Summary: Age at puberty is a main factor affecting reproductive efficiency and, thus, livestock production. Besides species and breed, nutrition during growth plays a crucial role in the attainment of puberty. Controversial results are reported about the critical period during which heifers are more sensitive to the effects of nutrition on pubertal acceleration. Numerous papers are available about such topics, but they are characterized by very different experimental conditions (such as genetics, feeds, planes of nutrition, season and pasture quality, time windows, and parameters considered), making difficult the comparison among inconstant results by various trials. Several indicators during growth have been proposed as predictors of age at puberty, such as body weight gains, body fat reserves, and linear body measurements. Blood concentrations of hormones strictly linked to growth and reproduction have also been considered: higher Insulin-like Growth Factor-1 levels are reported to be related to earlier puberty, while leptin is not. More uniform experimental conditions should be encouraged for future research. 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. [ABSTRACT FROM AUTHOR]

Women with gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), and preterm birth (PTB) have excess cardiovascular disease compared with those with uncomplicated births, perhaps related to prepregnancy inflammation, dysmetabolism, or endothelial dysfunction. We included 1238 women in the Coronary Artery Risk Development in Young Adults Study (1985-2011) with 2215 births classified according to outcomes (term, uncomplicated births were the referent). Using repeated measures analysis of variance, we estimated prepregnancy and postpregnancy biomarkers, as well as biomarker change according to pregnancy outcomes, adjusted for confounders. GDM and term HDP groups had higher prepregnancy high-sensitivity C-reactive protein (hsCRP) (+0.37 [95% CI, 0.08-0.65]; +0.29 [95% CI, 0.04-0.55] log mg/L), higher leptin (+0.29 [95% CI, 0.09-0.50]; +0.37 [95% CI, 0.17-0.56] log ng/ml), and lower adiponectin (−0.25 [95% CI, −0.36 to −0.13); −0.11 [95% CI, −0.22 to −0.01] log ng/ml) values than those with uncomplicated births, and these profiles persisted in magnitude postpregnancy. Controlling for body mass index attenuated most profiles, except that lower prepregnancy adiponectin remained associated with GDM. PTB without HDP or GDM was related to lower prepregnancy hsCRP and soluble intercellular adhesion molecule-1 (−0.31 [95% CI, −0.56 to −0.06] log mg/L; −0.05 [95% CI, −0.09 to −0.01] log ng/ml) and a larger leptin increase from before to after pregnancy (+0.20 [95% CI, 0.02-0.37] log ng/ml). Prepregnancy inflammation and metabolic dysfunction contributed to GDM and HDP, perhaps due to higher body mass index. PTB may be related to adverse metabolic changes postpregnancy, although the unexpected endothelial biomarker profile warrants further study. [ABSTRACT FROM AUTHOR]

Recent molecular biological and electrophysiological studies have identified multiple transient receptor potential (TRP) channels in hypothalamic neurons as critical modulators of homeostatic functions. In particular, the canonical transient receptor potential channels (TRPCs) are expressed in hypothalamic neurons that are vital for the control of fertility and energy homeostasis. Classical neurotransmitters such as serotonin and glutamate and peptide neurotransmitters such as kisspeptin, neurokinin B and pituitary adenylyl cyclase‐activating polypeptide signal through their cognate G protein‐coupled receptors to activate TPRC 4, 5 channels, which are essentially ligand‐gated calcium channels. In addition to neurotransmitters, circulating hormones like insulin and leptin signal through insulin receptor (InsR) and leptin receptor (LRb), respectively, to activate TRPC 5 channels in hypothalamic arcuate nucleus pro‐opiomelanocortin (POMC) and kisspeptin (arcuate Kiss1 [Kiss1ARH]) neurons to have profound physiological (excitatory) effects. Besides its overt depolarizing effects, TRPC channels conduct calcium ions into the cytoplasm, which has a plethora of downstream effects. Moreover, not only the expression of Trpc5 mRNA but also the coupling of receptors to TRPC 5 channel opening are regulated in different physiological states. In particular, the mRNA expression of Trpc5 is highly regulated in kisspeptin neurons by circulating estrogens, which ultimately dictates the firing pattern of kisspeptin neurons. In obesity states, InsRs are "uncoupled" from opening TRPC 5 channels in POMC neurons, rendering them less excitable. Therefore, in this review, we will focus on the critical role of TRPC 5 channels in regulating the excitability of Kiss1ARH and POMC neurons in different physiological and pathological states. [ABSTRACT FROM AUTHOR]

Adipokines play essential roles in regulating a range of biological processes, but growing evidence indicates that they are also fundamental in immunological mechanisms and, primarily, inflammatory responses. Adipokines mediate their actions through specific receptors. However, although adipokine receptors are widely distributed in many cell and tissue types, limited data are available on their expression in mast cells (MCs) and, consequently, adipokine's significance in the modulation of MC activity within the tissues. In this study, we demonstrate that rat peritoneal MCs constitutively express the leptin receptor (i.e. LEPR), adiponectin receptors (i.e. ADIPOR1 and ADIPOR2) and the chemerin receptor (i.e. CMKLR1). We also found that LEPR, ADIPOR1, ADIPOR2 and CMKLR1 expression in MCs changes in response to stimulation by their specific ligands and some cytokines with potent proinflammatory properties. Furthermore, the involvement of intracellular signaling molecules in leptin‐, adiponectin‐ and chemerin‐induced MC response was analyzed. Overall, our findings suggest that adipokines leptin, adiponectin and chemerin can significantly affect the activity of MCs in various processes, especially during inflammation. These observations may contribute significantly to understanding the relationship between adipokines, immune mechanisms and diseases or conditions with an inflammatory component. [ABSTRACT FROM AUTHOR]

Dormancy is an essential ecological characteristic for the survival of organisms that experience harsh environments. Although factors that initiate dormancy vary, suppression or cessation of feeding activities are common among taxa. To distinguish between extrinsic and intrinsic causes of metabolic reduction, we focused on estivation, which occurs in summer when the feeding activity is generally enhanced. Sand lances (genus Ammodytes) are a unique marine fish with a long estivation period from early summer to late autumn. In the present study, we aimed to elucidate the control mechanisms of estivation in western sand lance (A. japonicus), and firstly examined behavioral changes in 8 months including a transition between active and dormant phases. We found that swimming/feeding behavior gradually decreased from June, and completely disappeared by late August, indicating all individuals had entered estivation. Next, we focused on leptin, known as a feeding suppression hormone in various organisms, and examined leptin‐A gene (AjLepA) expression in the brain that may regulate the seasonal behavioral pattern. AjLepA expression decreased after 7 days of fasting, suggesting that leptin has a function to regulate feeding in this species. The monthly expression dynamics of AjLepA during the feeding (active) and non‐feeding (estivation) periods showed that the levels gradually increased with the onset of estivation and reached its peak when all the experimental fish had estivated. The present study suggests that the suppression of feeding activity by leptin causes shift in the physiological modes of A. japonicus before estivation. Research highlights: Sand lance spends in sand for more than half a year without feeding, a unique dormancy among teleosts called estivationLeptin, a peptide hormone, was found to be involved in appetite suppression in brain and work to exert the onset of estivation [ABSTRACT FROM AUTHOR]

Sedentary behavior (SB) has been linked to risk factors of cardiometabolic disease, with inconsistent findings reported in the literature. We aimed to assess the associations of SB with multiple biomarkers of inflammation and insulin resistance in adults. Domain-specific SB, sitting time and moderate-to-vigorous physical activity (MVPA) were measured in 78 adults (mean ± SD 52.0 ± 10.8 y). Body fat percentage (BF%) was assessed using multi-frequency bioelectrical impedance. A blood draw assessed glucose, insulin, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), leptin, and adiponectin. Adiponectin-leptin ratio (ALR), homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β) were calculated. Multivariable linear regression analyses, controlling for age, sex, MVPA, and BF%, were used to assess associations. After adjustment for age, sex and MVPA, total SB (7.5 ± 2.5 h/day) was positively associated with leptin, insulin, HOMA-IR, HOMA-β (Standardized Beta (β) range 0.21–0.32) and negatively associated with ALR (β = -0.24, p < 0.05 for all). Similarly, total sitting time (7.2 ± 2.9 h/day) was associated with TNF-α (β = 0.22) and ALR (β = -0.26). These associations were attenuated to non-significance after adjustment for BF%. Leisure screen time was detrimentally associated with IL-6 (β = 0.24), leptin (β = 0.21), insulin (β = 0.37), HOMA-IR (β = 0.37), and HOMA-β (β = 0.34), independent of age, sex and MVPA (p < 0.05 for all). Only the associations with insulin (β = 0.26), HOMA-IR (β = 0.26), and HOMA-β (β = 0.23) remained significant after further controlling BF% (p < 0.05). Self-reported SB is associated with biomarkers of inflammation and insulin resistance, independent of MVPA, and in some cases BF%. [ABSTRACT FROM AUTHOR]

Background: Chewing Khat (Catha edulis) releases cathine and cathinone, which may reduce appetite via an unknown mechanism. This study investigated the peripheral and central effects of fresh leaves and buds of Catha edulis water extract (CEWE) on appetite biomarkers, gene expression, and body weight, using in vivo, ex vivo, and in silico models. Methods: Rats of both sexes were orally administered CEWE at different doses and durations in three different experiments. Liquid chromatography-mass spectroscopy (LC-MS)-MS was used to detect cathinone and cathine in the murine blood. The effect of Khat on serotonin receptors was studied in isolated rat fundus samples. Docking of the two Khat ligands was performed on G (The 5-hydroxytryptamine-type 2C receptor (5-HT2C) in an agonist-bound active conformation) and H (5-HT2C in an antagonist-bound inactive conformation) proteins to determine which ligands are most likely to act as agonists or antagonists. Results: Significant differences (P < 0.05) in body weight were observed between the CEWE-treated groups and the controls over eight weeks. However, the plasma leptin and ghrelin levels did not change significantly (P > 0.05). The expression of the ghrelin and leptin genes was also unaffected, but the expression of the 5-hydroxytryptamine (5-HT) gene decreased (P < 0.05) with CEWE treatment. CEWE antagonizes 5-HT receptors in isolated rat fundus samples. Docking findings indicated that the khat ligands bound to 5-HT2C receptors. Cathine and cathinone levels in rat plasma were measured. Conclusion: Khat extract may suppress appetite by antagonizing the 5-HT receptors. Further research is required to understand its mechanism and potential applications. [ABSTRACT FROM AUTHOR]

• VPA therapy for six months resulted in insulin resistance, alteration in weight, and metabolic hormones (leptin and adiponectin). • These changes were independent of serum level or pharmacokinetic of VPA. • In LEV group, no such changes were observed despite increased serum LEV level and decreased Vd and CL of LEV after six months of therapy. • These findings may be considered for optimization of ASM treatment regimen in adult patients with obesity or metabolic dysfunctions. To evaluate the incidence of insulin resistance and its association with change in serum anti-seizure medication (ASM) level and their pharmacokinetic, body composition and metabolic hormones after six months of levetiracetam (LEV) exposure in persons with epilepsy (PWE) in comparison to valproate (VPA). This prospective-longitudinal study included clinically diagnosed PWE on VPA or LEV monotherapy (for<3 months). At enrolment, body weight/composition, BMI were measured and blood samples were collected for assessing metabolic dysfunctions by estimation of serum insulin, insulin resistance [in terms of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)], leptin, adiponectin, lipid profile along with ASMs level. Subjects were followed up for six months and all the above parameters were reassessed. A total of 150 PWE were screened based on inclusion and exclusion criteria, and 105 number of subjects were enrolled (n = 35 in VPA and n = 70 in LEV group). Out of them, 92 subjects (n = 32 in VPA; n = 60 in LEV) completed six months follow-up. After six months, serum insulin level increased significantly in VPA group compared to baseline p < 0.001). Insulin resistance (HOMA-IR>2.5) was observed in 14.28 % of PWE in VPA group. Significantly higher percentage-change in body-weight (p = 0.003), leptin and decreased adiponectin were found in VPA-group compared to baseline ((p = 0.003, 0.02, 0.001, <0.001, respectively). These changes were independent of serum level or pharmacokinetic of VPA. On the other hand, no such changes were observed in LEV-group despite increased serum LEV level and altered pharmacokinetic parameters after six months. Six months treatment with VPA resulted in insulin resistance and metabolic dysfunctions in PWE. These alterations were not correlated with change in VPA serum level. These changes were not observed in LEV therapy suggesting its better safety profile. This may be considered while prescribing the ASM like VPA and LEV in adult patients with obesity or insulin resistance and diabetes. [ABSTRACT FROM AUTHOR]

The stage of life at the onset of obesity is an important factor in assessing inflammatory state and cardiometabolic risk. This study aimed to evaluate the relationship between the obesity onset and the inflammatory profile in women with severe obesity. Public hospital, Brazil. Forty-eight women with severe obesity (20–59 yr old) were evaluated according to weight, height, neck circumference (NC), waist circumference (WC), and hip circumference, as well blood metabolic and inflammatory parameters. The participants were grouped according to obesity onset stage of life (early group: ≤19 yr; late group: >19 yr). The demographic means of the participants were: age of 39.7 years, weight of 122.7 kg and body mass index (BMI) of 48.4 kg/m2. The late group presented significantly higher values of leptin (lep)/adiponectin (adipo) ratio and homeostatic model assessment for insulin resistance (HOMA-IR) than the early group. The late group also had a lower adipo/lep ratio. Moreover, the late group showed correlations between the lep/adipo ratio and BMI (r =.460, P =.021), NC (r =.478, P =.016), and WC (r =.535, P =.006). Adipo was also correlated with NC (r = −.418, P =.038), WC (r = −.437, P =.029), and glycated hemoglobin (HbA1C) (r = −.485, P =.019). By contrast, in the early group, the lep/adipo ratio showed correlations with insulin (r =.647, P =.004) and HOMA-B (r =.564, P =.015). The inflammatory profile is correlated with anthropometric values in women with late-onset obesity. Inflammatory markers seemed to correlate with the glycemic profile in women with early-onset obesity. Furthermore, inflammation was higher in women with late-onset obesity compared to those with early-onset obesity. • First study to report the correlation of time of obesity onset and inflammation. • The study was performed only on women with severe obesity. • New insights were found regarding inflammation and obesity onset. • New findings were obtained regarding glycemic profile and obesity onset. [ABSTRACT FROM AUTHOR]

Background: Inflammation plays a central role in many chronic diseases that characterize modern society. Leptin/adiponectin and adiponectin/leptin ratios have been recognized as notable markers of dysfunctional adipose tissue and, consequently, an inflammatory state. Methods: Blood samples were collected from 41 adult volunteers (40.2 ± 8.3 years) diagnosed with severe obesity (BMI 46.99; 42.98–51.91 kg/m2). The adipokines were quantified using an enzyme-linked immunosorbent assay, while the serum fatty acid analysis was conducted using chromatography. Results: The results unveiled a positive correlation between the leptin/adiponectin ratio and the 20:3n6 fatty acid (r = 0.52, p = 0.001), as well as a similar positive correlation between the adiponectin/leptin ratio and the 22:6n3 fatty acid (r = 0.74, p = 0.001). In the regression analysis, the 22:6n3 fatty acid predicted the adiponectin/leptin ratio (β = 0.76, p < 0.001), whereas C20:3 n-6 was a predictor for inflammatory markers (β = 4.84, p < 0.001). Conclusions: In conclusion, the 22:6n3 fatty acid was demonstrated to be a predictive factor for the adiponectin/leptin ratio and C20:3 n-6 was a predictor for inflammatory markers. This discovery, novel within this population, can help develop new intervention strategies aimed at controlling the inflammatory status in individuals classified as having severe obesity. [ABSTRACT FROM AUTHOR]

Purpose Biallelic pathogenic leptin gene variants cause severe early-onset obesity usually associated with low or undetectable circulating leptin levels. Recently, variants have been described resulting in secreted mutant forms of the hormone leptin with either biologically inactive or antagonistic properties. Methods We conducted a systematic literature research supplemented by unpublished data from patients at our center as well as new in vitro analyses to provide a systematic classification of congenital leptin deficiency based on the molecular and functional characteristics of the underlying leptin variants and investigated the correlation of disease subtype with severity of the clinical phenotype. Results A total of 28 distinct homozygous leptin variants were identified in 148 patients. The identified variants can be divided into 3 different subtypes of congenital leptin deficiency: classical hormone deficiency (21 variants in 128 patients), biologically inactive hormone (3 variants in 12 patients), and antagonistic hormone (3 variants in 7 patients). Only 1 variant (n = 1 patient) remained unclassified. Patients with biological inactive leptin have a higher percentage of 95th body mass index percentile compared to patients with classical hormone deficiency. While patients with both classical hormone deficiency and biological inactive hormone can be treated with the same starting dose of metreleptin, patients with antagonistic hormone need a variant-tailored treatment approach to overcome the antagonistic properties of the variant leptin. Main Conclusion Categorization of leptin variants based on molecular and functional characteristics helps to determine the most adequate approach to treatment of patients with congenital leptin deficiency. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Recent studies have highlighted leptin, a key hormone that regulates energy intake and induces satiety, due to the worldwide prevalence of obesity. In this study, we analyzed plasma leptin measurements from 18 women with premenopausal obesity before and after bromocriptine treatment. By using underlying pulses recovered through deconvolution, we modeled the leptin secretory pulses as marked point processes and applied statistical distributions to evaluate the dynamics of leptin, including the interpulse intervals and amplitudes of the secretion. We fit the generalized inverse Gaussian and lognormal distributions to the intervals and the Gaussian, lognormal, and gamma distributions to the amplitudes of pulses. We evaluated the models' goodness of fit using statistical metrics including Akaike's information criterion, Kolmogorov-Smirnov plots, and quantile-quantile plots. Our evaluation results revealed the effectiveness of these statistical distributions in modeling leptin secretion. Although the lognormal and gamma distributions performed the best based on the metrics, we found all distributions capable of accurately modeling the timing of secretory events, leading us to a better understanding of the physiology of leptin secretion and providing a basis for leptin monitoring. In terms of pulse amplitude, the evaluation metrics indicated the gamma distribution as the most accurate statistical representation. We found no statistically significant effect of bromocriptine intake on the model parameters except for one distribution model. [ABSTRACT FROM AUTHOR]

AbstractThe efficacy of probiotics, prebiotics, or synbiotics in children and adolescents with overweight or obesity remains uncertain. This systematic review evaluates their intervention effects through a network meta-analysis of randomized clinical trials (RCTs). Searches of 4 electronic databases until January 7, 2024, yielded 17 papers reporting on 15 RCTs involving 820 participants. Multiple-strain probiotics (MSP) showed significant efficacy in reducing BMI (Mean Difference (MD) −2.13 kg/m2, 95% credible interval (CrI) [−2.7, −1.57]), waist circumference (MD −1.34 cm, 95% CrI [−2.33, −0.35]), total cholesterol (MD −6.55 mg/dL, 95% CrI [−10.61, −2.45]), triglycerides (MD −3.71 mg/dL, 95% CrI [−5.76, −1.67]), leptin (MD −3.99 ng/mL, 95% CrI [−4.68, −3.3]), and hypersensitive C-reactive protein (Hs-CRP) (MD −1.21 mg/L, 95% CrI [−1.45, −0.97]). Synbiotics were effective in reducing BMI-z score (MD −0.07, 95% CrI [−0.10, −0.04]) and LDL-C (MD −1.54 mg/dL, 95% CrI [−1.98, −1.09]) but led to a slight increase in fasting glucose (MD 1.12 mg/dL, 95% CrI [0.75, 1.49]). Single-ingredient prebiotics and single-strain probiotics also had some beneficial effects on BMI and Hs-CRP, respectively. Moderate to low evidence suggests MSP may be a potential choice for improving BMI and reducing lipids, leptin, and Hs-CRP levels, implying that MSP could aid in managing pediatric obesity and related metabolic issues by modulating the gut microbiota. Although synbiotics show their favorable effects on body metrics and lipid control, their potential impact on blood glucose currently prevents them from being an alternative to MSP for treating pediatric obesity. Further large-scale, well-designed studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Objective. The importance of early microbial dysbiosis in later development of obesity and metabolic disorders has been a subject of debate. Here we tested cause and effect in mice. Methods. Germ‐free male Swiss Webster mice were colonized in a specific‐pathogen‐free (SPF) facility at 1 week (1W) and 3 weeks (3W) of age. They were challenged with a high‐fat diet and their responses were compared with SPF mice. Gut microbiota was analyzed by 16S rRNA gene sequencing. Moreover, RNA sequencing of the liver was performed on additional 3W and SPF mice on a regular chow diet. Results. There were no significant differences in weight, food consumption, epididymal fat weight, HbA1c levels, and serum insulin and leptin, whereas the early germ‐free period resulted in mice with impaired glucose tolerance. Both the 1W and 3W group peaked 56% (p < 0.05) and 66% (p < 0.01) higher in blood glucose than the SPF control group, respectively. This was accompanied by a 45% reduction in the level of the anti‐inflammatory cytokine IL‐10 in the 1W mice (p < 0.05). There were no differences in the gut microbiota between the groups, indicating that all mice colonized fully after the germ‐free period. Marked effects on hepatic gene expression (728 differentially expressed genes with adjusted p < 0.05 and a fold change ± 1.5) suggested a potential predisposition to a higher risk of developing insulin resistance in the 3W group. Conclusions. Lack of microbes early in life had no impact on adiposity but led to insulin resistance and altered liver gene expression related to glucose metabolism in mice. The study strongly supports the notion that microbial signaling to the liver in the beginning of life can alter the host's risk of developing metabolic disorder later in life. [ABSTRACT FROM AUTHOR]

Background: Cancer-associated fibroblasts, as a major component of the tumor microenvironment, have been shown to exhibit protumorigenic effects in pancreatic ductal adenocarcinoma. Moreover, cancer-associated fibroblasts-derived exosomes have been reported to promote tumor development, but exact mechanisms have not been elucidated. The purpose of this study was to investigate the processes by which exosomes generated from cancer-associated fibroblasts promote tumor growth. Methods: twenty-one patients with pancreatic ductal adenocarcinoma who evaluated preoperatively as potentially surgically resectable without distant metastasis and pathologically examined postoperatively as pancreatic ductal cell carcinoma were included. We determined the expression of Leptin as well as downstream proteins at the clinical and cellular levels. Cancer-associated fibroblast-derived exosomes were characterised by nanoparticle transmission electron microscopy and tracking analysis. To ascertain the mechanism mediating the action of exosomal Leptin in pancreatic ductal adenocarcinoma, we performed CCK-8 assay, colony formation assays, transwell and wound healing assays in PSN1 cells to evaluate cell proliferation, migration and invasion. Western blotting was used to detect the level of Leptin, ABL2 and exosome markers. qRT-PCR was employed to evaluate miR-224-3p. Cancer-associated fibroblasts markers and exosome uptake were verified by immunofluorescence. Results: Western blotting assays show that Leptin is present inside tissues and cancer-associated fibroblasts in pancreatic ductal adenocarcinoma. Cancer-associated fibroblasts stimulated PSN1 cells growth, migration and invasion in vitro by secreting the exosomal Leptin. Exosomal Leptin could regulate miR-224-3p, which targets negative regulation of ABL2. Inhibiting Leptin significantly limited PSN1 cells growth, migration and invasion. In vitro analyses revealed that miR-224-3p mimics mitigate the inhibitory effect of cancer-associated fibroblasts knockdown of Leptin on PSN1 cells development, but overexpression of ABL2 partly abolished the tumor-promoting phenotype of miR-224-3p mimics. Conclusion: Our results revealed that cancer-associated fibroblasts mediate pancreatic ductal adenocarcinoma development by regulating the miR-224-3p/ABL2 molecular axis through the secretion of the exosomal Leptin. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) severely impairs skin wound healing capacity, yet few treatment options exist to enhance this process. N-acetylcysteine (NAC) is an antioxidant that improves cellular proliferation and enhances wound healing in healthy animals, yet its use in the context of type II DM has not been studied. The aim of our research was to investigate the effect of topically applied NAC-enriched hydrogels on wound healing in a leptin-deficient murine wound model. Four excisional wounds were created on the backs of 20 db/db mice and were subsequently treated with hydrogels containing NAC at concentrations of 5%, 10% and 20% or placebo (control). Healing was monitored for 28 days; photographs of the wounds were taken on every third day. Wound tissues were harvested on days 3, 7, 14 and 28 to undergo histological examinations. Wounds treated with 5% NAC showed improved wound closure speed accompanied by an increased dermal proliferation area on microscopic assessment compared with other groups. Higher concentrations of NAC failed to show a beneficial effect on wound healing. 5% NAC improved early stages of wound healing in a murine model of type II DM by increasing wound closure speed, likely mediated by improved dermal proliferation. [ABSTRACT FROM AUTHOR]

Leptin is a hormone produced by the small intestines and adipose tissue that promotes feelings of satiety. Leptin receptors (LepRs) are highly expressed in the hypothalamus, enabling central neural control of hunger. Interestingly, LepRs are also expressed in several other regions of the body and brain, notably in the cerebral cortex and hippocampus. These brain regions mediate higher-order sensory, motor, cognitive, and memory functions, which can be profoundly altered during periods of hunger and satiety. However, LepR expression in these regions has not been fully characterized on a cell-type-specific basis, which is necessary to begin assessing their potential functional impact. Consequently, we examined LepR expression on neurons and glia in the forebrain using a LepR-Cre transgenic mouse model. LepR-positive cells were identified using a 'floxed' viral cell-filling approach and co-labeling immunohistochemically for cell-type-specific markers, i.e., NeuN, VGlut2, GAD67, parvalbumin, somatostatin, 5-HT3R, WFA, S100β, and GFAP. In the cortex, LepR-positive cells were localized to lower layers (primarily layer 6) and exhibited non-pyramidal cellular morphologies. The majority of cortical LepR-positive cells were neurons, while the remainder were identified primarily as astrocytes or other glial cells. The majority of cortical LepR-positive neurons co-expressed parvalbumin, while none expressed somatostatin or 5-HT3R. In contrast, all hippocampal LepR-positive cells were neuronal, with none co-expressing GFAP. These data suggest that leptin can potentially influence neural processing in forebrain regions associated with sensation and limbic-related functions. [ABSTRACT FROM AUTHOR]

Chalcones constitute an important group of natural compounds abundant in fruits and comestible plants. They are a subject of increasing interest because of their biological activities, including anti-diabetic and anti-obesity effects. The simple chalcone structural scaffold can be modified at multiple sites with different chemical moieties. Here, we generated an artificial chalcone, i.e., 3,5-dimethyl-2,4,6-trimethoxychalcone (TriMetChalc), derived from 2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC). DMC is a major compound of Cleistocalyx operculatus, a plant widely used in Asia for its anti-hyperglycemic activity. Using ob/ob mice as an obesity model, we report that, after 3 weeks of per os administration, TriMetChalc modified food intake through the specific activation of brain structures dedicated to the regulation of energy balance. TriMetChalc also decreased weight gain, glucose intolerance, and hepatic steatosis. Moreover, through extensive liver lipidomic analysis, we identified TriMetChalc-induced modifications that could contribute to improving the liver status of the animals. Hence, TriMetChalc is a chalcone derivative capable of reducing food intake and the addition of glucose intolerance and hepatic steatosis in a mouse model of obesity. In light of these results, we believe that TriMetChalc action deserves to be more deeply evaluated over longer treatment periods and/or in combination with other chalcones with protective effects on the liver. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumors (NETs) are a heterogeneous group of tumors that are characteristically different from other malignancies. The difference is not only in the prognosis, which is usually more favorable in such patients, but also in the high clinical progression of the disease, where NET patients do not experience the cachexia typical of other malignancies. The purposes of this study were to evaluate the ghrelin and leptin levels in a group of patients diagnosed with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and bronchopulmonary neuroendocrine tumors (BP-NETs) and to analyze the relationship between the body mass index (BMI), cachexia and selected NET markers. The study group comprised 52 patients with GEP-NETs and BP-NETs, while the controls comprised 67 healthy volunteers. The ghrelin and leptin concentrations were determined in both groups. The concentrations of chromogranin A, serotonin, 5-hydroxyindoleacetic acid (5-HIAA), total cholesterol, triglycerides and glucose were determined in the study group. Characteristics of the study group and of the controls were defined by age, sex and BMI, and the effects of these factors on the ghrelin and leptin concentrations were assessed. The data obtained were subject to statistical analysis. The study cohort showed higher levels of ghrelin as compared to the controls (142.31 ± 26.00 vs. 121.49 ± 35.45, p = 0.016), and no statistical difference in the levels of leptin (11.15 ± 9.6 vs. 12.94 ± 20.30, p = 0.439) were observed. Significantly lower levels of leptin were found in patients with the small intestine primary location, as compared to individuals with primary locations in the lungs and the pancreas (4.9 ± 6.49 vs. 16.97 ± 15.76, p = 0.045, and 4.9 ± 6.49 vs. 12.89 ± 8.56, p = 0.016, respectively). A positive correlation was observed between the leptin levels and the BMIs in both the study group (rS = 0.33, p = 0.016) and the controls (rS = 0.41, p = 0.001). The study group showed a negative correlation between the leptin levels and 5-HIAA (rS = −0.32, p = 0.026) and a negative correlation between the leptin levels and Ki-67 (rS = −0.33, p = 0.018). The control group showed negative correlations between the ghrelin and the volunteer age (rS = −0.41, p = 0.008), the leptin and the volunteer age (rS = −0.44, p < 0.001), the leptin and total cholesterol (rS = −0.24, p < 0.049) as well as the leptin and triglycerides (rS = −0.33, p < 0.006). The current study emphasized the importance of the markers' determination, where ghrelin appears as a valuable diagnostic biomarker in NETs, probably responsible for maintaining a normal BMI, despite the progression of the disease. [ABSTRACT FROM AUTHOR]

Background: The formation of macrosomia is associated with excessive nutrition and/or unable to regulate effectively. This case-control study aims to explore the relationship between macrosomia and glucose, lipids and hormones levels in maternal and cord serum. Methods: In the case-control study, 78 pairs of mothers and newborns were recruited who received care at one hospital of Hebei, China between 2016 and 2019. According to the birth weight (BW) of newborns, participants were divided into macrosomia group (BW ≥ 4000 g, n = 39) and control group (BW between 2500 g and 3999 g, n = 39). Maternal vein blood and cord vein blood were collected and assayed. All data were compared between the two groups. Unconditional logistics regression analysis was used to test the relationship between macrosomia and glucose, lipids and hormones in maternal and cord serum. Results: In maternal and cord serum, the levels of leptin, leptin/adiponectin ratio (LAR), glucose and triglyceride (TG) in macrosomia group were higher than those in control group, and the levels of high-density lipoprotein cholesterol (HDL-C) were lower. The percentage of maternal glucose and lipids transfer to cord blood did not differ between the two groups. High levels of TG in maternal serum were positively correlated with macrosomia, and high levels of LAR, TG and glucose in cord serum were positively correlated with macrosomia. Conclusion: In conclusion, the results of the current study, suggest that the nutrients and metabolism-related hormones in maternal and umbilical cord are closely related to macrosomia. During pregnancy, the nutritional status of pregnant women should be paid attention to and to obtain a good birth outcome. [ABSTRACT FROM AUTHOR]

Introduction: Depression therapy has been linked to negative effects on energy metabolism, which can be attributed to various factors, including an ongoing inflammatory process commonly seen in metabolic disorders. Unhealthy lifestyle choices of patients and the impact of antidepressants on body weight and lipid and glucose metabolism also contribute to these metabolic side effects. Although not as pronounced as other psychopharmaceuticals, the increasing use of antidepressants raises concerns about their potential impact on public health. The study aimed to evaluate the short- and long-term effects of the antidepressant citalopram and its long-term combination with a special diet on metabolic parameters in mice. Methods: Animals were randomly divided into 5 groups – control, control + special diet, citalopram (10 mg/kg for 35 days), citalopram + special diet (10 mg/kg for 35 days), and citalopram (10 mg/kg for 7 days). After a described time of administration, animals were anesthetized, blood and fat and liver tissues were collected. Biochemical parameters of lipid metabolism (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) and glucose were analyzed using spectrophotometry and relevant adipokines and cytokines were evaluated by ELISA. Results: After a week of application of citalopram, we observed dyslipidemia that persisted even at the end of the 5-week experiment. Furthermore, after 5 weeks of citalopram administration, we observed a significant decrease in body weight gain and decreased leptin levels. Changes in lipid metabolism, higher levels of adipokines leptin and PAI-1 were observed due to the special diet after 5 weeks. Conclusions: Our research suggests that the effects of citalopram and a diet on the metabolism of mice can be significant, both in the short term (1 week) and in the long term (5 weeks). [ABSTRACT FROM AUTHOR]

Background: Carboxylesterase 1(CES1) is expressed mainly in the liver and adipose tissue and is highly hypothesized to play an essential role in metabolism. Our study aimed to investigate the association between CES1 and metabolic syndrome (MetS) and metabolic dysfunction associated steatotic liver disease (MASLD) in children with obesity in China. Methods: This study included 72 children with obesity aged 6-13years (including 25(35%) diagnosed as MetS and 36(50%) diagnosed as MASLD). All subjects were measured in anthropometry, serum level of biochemical parameters related to obesity, circumstance levels of insulin-like growth factor1, adipokines (adiponectin, leptin and growth differentiation factor 15) and CES1. Results: Higher serum CES1 level were found in the MetS group (P = 0.004) and the MASLD group (P < 0.001) of children with obesity. Serum CES1 levels were positively correlated with alanine aminotransferase, aspartate aminotransferase, triglyceride, cholesterol, low-density lipoprotein cholesterol, GDF15, Leptin and negatively correlated with high-density lipoprotein cholesterol, adiponectin and IGF1. We also found a multivariable logistic regression analysis of MASLD and MetS predicted by CES1 significantly (MASLD P < 0.01, MetS P < 0.05). The combination of CES1, sex, age and BMI Z-score showed a sensitivity and specificity of 92.7% for the identification of MASLD and 78.6% for the identification of MetS. The cutoff for CES1 of MASLD is 56.30 ng/mL and of MetS is 97.79 ng/mL. Conclusions: CES1 is associated with an increasing risk of MetS and MASLD and can be established as a biomarker for metabolic syndrome and MASLD of children with obesity. [ABSTRACT FROM AUTHOR]

Background: Beneficial effects from practising a Paleolithic diet as compared to a diabetes diet on weight, waist circumference, satiety, leptin, HbA1c and glucose control in randomised controlled trial participants with type 2 diabetes could be due to lower leptin resistance. Support for this hypothesis comes from an in vitro experiment that showed that digested wheat gluten, which is excluded from a Paleolithic diet, inhibits leptin from binding to its receptor, thus indicating a possible dietary cause of leptin resistance. However, the clinical relevance of the latter finding is unclear since removal of enzyme activity from the gluten digest by heat treatment also abolished leptin binding inhibition. Assessment of leptin binding inhibition in vivo is possible by comparison of total leptin levels with those of 'biologically active' leptin bound to its receptor (bioLep). Objectives: To assess the effects of a Paleolithic diet compared to a diabetes diet on leptin binding inhibition and to replicate our in vitro study. Methods: BioLep and total leptin levels were measured in secondary analysis of fasting plasma samples from our open label random order three plus three-month long cross-over trial performed in 2005–2007, that compared a Paleolithic diet with a diabetes diet in participants with type 2 diabetes without insulin treatment (per protocol). BioLep was also measured in vitro for known recombinant leptin concentrations incubated with a series of concentrations of 10 kDa spin-filtered digested wheat gluten, with or without prior heat treatment, at 100ºC for 30 min and centrifugation. Results: There was no difference between diets when comparing differences between bioLep and total leptin levels and their ratio in the 13 participants, three women and 10 men, aged 52–74 years with a mean BMI of 30 kg/m2 and a mean diabetes duration of eight years. We found no carry-over or period effect for bioLep and total leptin. In vitro, wheat gluten digest inhibited leptin binding in a dose-dependent manner but not after heat treatment. Conclusions: We found no leptin binding inhibition after the Paleolithic or diabetes diet, possibly due to its abolishment from cooking-related heat treatment of wheat gluten. Trial registration: Registered on 14/02/2007 at ClinicalTrials.gov Identifier: NCT00435240. [ABSTRACT FROM AUTHOR]

Background: Infertility is a growing global health concern affecting millions of couples worldwide. Among several factors, an extreme body weight adversely affects reproductive functions. Leptin is a well-known adipokine that serves as an endocrine signal between adiposity and fertility. However, the exact mechanisms underlying the effects of high leptin level on female reproduction remain unclear. Methods: Transgenic pigs overexpressing leptin (♀) were produced by backcrossing and screened for leptin overexpression. The growth curve, fat deposition, reproductive performance, apoptosis, serum hormones and cholesterol production, RNA sequencing, and single-nucleus RNA sequencing (snRNA-seq) of the leptin-overexpressing pigs and wild-type group were evaluated. Results: Transgenic pigs overexpressing leptin (♀) were obtained, which exhibited significantly reduced body weight, body size, and back fat thickness. These pigs manifested a late onset of puberty (330 ± 54.3 vs. 155 ± 14.7 days), irregular estrous behavior characterized by increased inter-estrous interval (29.2 ± 0 vs. 21.3 ± 0.7 days), and more number of matings until pregnancy (at least 3 times). This reproductive impairment in leptin pigs was related to hormonal imbalances characterized by increased levels of FSH, LH, prolactin, E2, P4, and TSH, altered steroidogenesis such as increased levels of serum cholesterol esters along with steroidogenic markers (StAR, CYP19A), and ovarian dysfunctions manifested by neutrophilic infiltration and low expression of caspase-3 positive cells in the ovaries. Moreover, bulk RNA sequencing of the ovaries also revealed neutrophilic infiltration followed by upregulation of inflammation-related genes. Furthermore, snRNA-seq reflected that leptin overexpression triggered immune response, suppressed follicle development and luteinization, resulting in metabolic dysfunction and hormone imbalance in the ovary. Conclusions: Low body weight in leptin overexpressing pigs adversely affects the reproductive performance, causing delayed puberty, irregular estrous cycles, and reduced breeding efficiency. This is linked to metabolic imbalances, an increased immune response, and altered ovarian functions. This study provides a theoretical basis for the complex mechanisms underlying leptin, and infertility by employing leptin-overexpressing female pigs. [ABSTRACT FROM AUTHOR]

Diabetic vascular disease is a major complication of diabetes mellitus (DM). Chemokine C-C motif ligand 7 (CCL7) attracts macrophages and monocytes, amplifying inflammatory processes in the vasculature. We hypothesized a causal role for CCL7 in diabetic vasculopathy. CCL7 concentrations were higher in the plasma of patients with type 2 DM, as well as in supernatants from their endothelial progenitor cells (EPCs). High-glucose stimulation increased the secretion of CCL7 from human dermal microvascular endothelial cells (HDMECs) through the c-Fos and c-Jun signaling pathways. CCL7 inhibition using knockdown or neutralization antibody treatment reversed the high glucose–induced impaired tube formation and migration abilities of EPCs, human aortic endothelial cells, human coronary artery endothelial cells, and HDMECs. Administration of recombinant human CCL7 protein impaired tube formation and migration abilities by down-regulating the AKT–endothelial nitric oxide synthase and AKT/nuclear factor erythroid 2–related factor 2/heme oxygenase–1/vascular endothelial growth factor/stromal cell–derived factor–1 pathways and by up-regulating ERK/phosphorylated p65/interleukin-1β/interleukin-6/tumor necrosis factor–α pathways through CC chemokine receptor 3 in endothelial cells. Ccl7 knockout in streptozotocin-treated mice showed improved neovasculogenesis in ischemic limbs and accelerated wound repair, with increased circulating EPCs and capillary density. CCL7 antibody treatment in db/db mice and high-fat diet–induced hyperglycemia mice showed improved neovasculogenesis in ischemic limbs and wound areas, accompanied by up-regulation of angiogenic proteins and down-regulation of inflammatory proteins. Endothelial cell–specific Ccl7-knockout mice showed ameliorated diabetic vasculopathy in streptozotocin-induced DM. This study highlights the potential of CCL7 as a therapeutic target for diabetic vasculopathy. Editor's summary: Diabetes can result in harmful vascular complications. It is not fully understood how inflammatory cells contribute to diabetic vasculopathy. Chang et al. showed that CCL7, an immune cell–recruiting factor, could be inhibited to improve vascular function in diabetes models. Inhibiting CCL7 in human cells promoted endothelial functions under high-glucose stress. In mouse models of diabetes including streptozotocin treatment, leptin receptor mutation, or high-fat diet feeding, CCL7 neutralization antibody treatment or genetic knockout improved blood flow recovery after experimental limb ischemia. Wound closure was also accelerated by CCL7 inhibition in each mouse model. Endothelial-specific CCL7 knockout had similar protective effects in streptozotocin-treated mice. These data suggest that CCL7 inhibition could be a therapeutic target for diabetic vasculopathy. —Brandon Berry [ABSTRACT FROM AUTHOR]

Background & Aims: Adipokines are among the biomarkers that have been studied in chronic pancreatitis (CP), as well as in pancreatic cancer (PC). So far, the existing findings are contradictory and inconclusive. Therefore, we assessed the levels of three major adipokines in CP in comparison to controls and PC, adiponectin, leptin, and resistin. Methods: A systematic electronic search was carried out in November 2022 using PubMed, Embase, and Scopus, reviewing observational studies. By using the Newcastle-Ottawa Scale, the included studies' quality was evaluated (NOS). In the examination of the estimated overall effect size, we employed the random-effects model in conjunction with the mean difference (MD) analysis. The MD with 95% confidence interval (CI) served as the primary summary outcome. Results: Our systematic review included a total of 14 studies, out of which nine were considered in our metaanalysis. A significant MD related to leptin levels in CP patients vs. controls (-1.299, 95%CI: -2.493 - -0.105), resistin levels in CP patients vs. controls (8.356, 95%CI: 3.700-13.012), and adiponectin levels in PC patients vs. controls (11.240, 95%CI: 5.872-16.60) was reported. However, no significant MD was reported in leptin levels between CP vs. PC patients (-0.936, 95%CI: -3.325-1.454), as well as adiponectin levels in CP patients vs. controls (0.422. 95%CI -5.651-6.535]) and in CP vs. PC patients (-6.252, 95%CI -13.269-0.766). Conclusions: CP was significantly associated with decreased leptin levels and increased resistin levels. Furthermore, increased levels of adiponectin are associated with PC. Yet, no significant MD was seen for leptin and adiponectin levels between CP and PC patients, and likewise for adiponectin levels between CP patients and controls. Results should be interpreted with caution due to the high heterogeneity among the included studies. [ABSTRACT FROM AUTHOR]

During pregnancy, the adipokines leptin and adiponectin can affect placental nutrient transport and inflammatory pathways, potentially leading to altered fetal growth and pregnancy complications including gestational diabetes mellitus (GDM) and preeclampsia (PE). The aim of this systematic review is to gather and analyze research on maternal circulating leptin and adiponectin levels and their relationship to adverse pregnancy and birth outcomes. Additionally, it seeks to determine whether these hormones are linked to alterations in placental transporters and cell signaling pathways. PubMed and MEDLINE were systematically searched to include studies published between 2012 and 2022. All primary data studies reporting serum adiponectin and/or leptin, placental mRNA and protein levels of related transporters, and adverse birth outcomes were eligible. The current systematic review encompasses a total of 14 articles. Abnormal serum maternal leptin and adiponectin levels were associated with changes in fetal growth and placental cellular signaling and nutrient transporters. A majority of studies associated elevated maternal leptin and reduced adiponectin with fetal overgrowth, although this relationship was not consistent and may be complicated when other pathologies are present. The effects of maternal leptin and adiponectin on fetal growth may be driven by placental adaptation in nutrient transporters and mitochondria. Future studies should determine if the placental effects of leptin and adiponectin that have been found in models have mechanistic roles in human pregnancy. [ABSTRACT FROM AUTHOR]

Introduction: Obesity is a prevalent co-morbidity in Polycystic Ovarian Syndrome (PCOS), causing metabolic disturbances that lead to changes in endocrinological homeostasis. Adipokines are proinflammatory molecules secreted by adipose tissues that affect metabolic and endocrinological mechanisms. Excess androgen secretion alters fat distribution and deposition, leading to increased visceral obesity in PCOS, which is a major concern for the development of cardiometabolic events. Aim: To assess the Visceral Adiposity Index (VAI) and levels of different adipokines in non obese and obese PCOS patients, and to establish the relationship between VAI and circulating adipokines in both non obese and obese phenotypes of PCOS patients. Materials and Methods: This cross-sectional study was conducted at the Mayo Institute of Medical Sciences, Barabanki, Uttar Pradesh, India from November 2019 to August 2021. A total of 144 patients diagnosed with PCOS according to the Rotterdam criteria were divided into non obese and obese categories based on Body Mass Index (BMI). VAI was calculated using a sex-specific formula, and serum levels of adiponectin, resistin, and leptin were measured by Enzyme Linked Immuno Sorbent Assay (ELISA). Fasting glucose, insulin, and serum lipid profiles were evaluated. Data were statistically analysed using Student's t-tests and Pearson's correlation coefficient. Weighted linear regression was used to detect any relationships between adipokines, obesity indicators, and VAI. Results: A total of 144 female patients with a mean age of 27.47±0.33 years suffering from PCOS were included in this study. VAI was significantly higher (p-value=0.034) in non obese patients than in obese patients. There was a significant correlation between VAI and resistin (r-value=0.302, p-value=0.011) and leptin (r-value=0.308, p-value=0.009) in the non obese PCOS group. Additionally, there was a significant association between obesity indicators {BMI, Body Fat Percentage (BFP), Waist Circumference (WC), and Hip Circumference (HC)} and VAI; this association was absent in the obese subgroup. According to the regression model, leptin was the only statistically relevant predictor for VAI among the studied PCOS patients (t-value=2.278, p-value=0.024). Conclusion: VAI was higher in non obese PCOS patients. An imbalance in adipokines (leptin and resistin) may lead to the accumulation of visceral fat without significantly affecting BMI. [ABSTRACT FROM AUTHOR]