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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., (© 2024. The Author(s).)

Weight gain variation is a great challenge in diet-induced obesity studies since low-gainer animals are of limited experimental value. The inbred C57BL/6 (B6) mice are frequently used models due to their genetic homogeneity and susceptibility to diet-induced obesity (DIO). The aim of this study is to investigate if the gut microbiota (GM) influences the fraction of low weight gainers in DIO studies. A total of 100 male B6 mice (donor population) were fed a high-fat diet for 14 weeks and divided into the study groups high gainer (HG) and low gainer (LG) based on their weight gain. Subsequently, fecal matter transplantation (FMT) was done on germ-free B6 mice with GM from HG and LG donors (FMT population). LG (13.35 ± 2.5 g) and HG (25.52 ± 2.0 g) animals were identified by the weight gain from week 1 to week 12. Interestingly, the start weight of the LG (20.36 ± 1.4 g) and HG (21.59 ± 0.7 g) groups differed significantly. Transplanting LG or HG fecal matter to germ-free mice resulted in significant differences in weight gain between HG and LG, as well as differences in serum leptin levels and epididymal fat pad weight. A clear LG-specific GM composition could not be distinguished by 16S rRNA gene amplicon sequencing. Surprisingly, significantly more fighting was recorded in LG groups of both donor populations and when transplanted to germ-free mice. The HG and LG phenotypes could be transferred to germ-free mice. The increased fighting in the LG group in both studies suggests not only that the tendency to fight can be transferred by FMT in these mice, but also that fighting should be prevented in DIO studies to minimize the number of LG animals., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Purpose: Weight regain after metabolic bariatric surgery is a common problem. Food addiction is an eating disorder that can be one of the reasons for weight regain in these patients. This study aimed to evaluate the effects of probiotic supplementation with a weight loss program and cognitive behavioral therapy (CBT) on anthropometric measures, eating behavior, food addiction, and related hormone levels, in patients with food addiction and weight regain after metabolic bariatric surgery., Materials and Methods: This randomized, triple-blind, placebo-controlled clinical trial was conducted on patients with food addiction and weight regain after metabolic bariatric surgery. Participants (n = 50) received a weight loss program and CBT plus probiotic, or placebo for 12 weeks. Then, anthropometric measurements, biochemical markers, eating behavior, and food addiction were assessed., Results: Weight and body mass index (BMI) decreased significantly in the probiotic group compared to placebo (p = 0.008, p = 0.001, respectively). Fat mass was significantly decreased in the probiotic group (p < 0.001). Moreover, a significant improvement was observed in the probiotic group's eating behavior and food addiction compared to the placebo group (p < 0.001). Serum levels of leptin decreased significantly (p = 0.02), and oxytocin serum levels increased significantly (p = 0.008) in the probiotic group compared to the placebo group., Conclusion: Adding probiotic supplements to the weight loss program and CBT is superior to the weight loss program and CBT alone in improving weight loss, eating behavior, and food addiction in patients with food addiction and weight regain after metabolic bariatric surgery., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Obesity has a detrimental impact on individuals, communities, and healthcare systems. Trefoil factor 3 is a secretory protein involved in metabolic processes related to weight regulation. However, its relation with obesity is not fully understood., Objective: We aimed to assess the serum trefoil factor 3 level and to immunohistochemical detect the leptin in obese patients to evaluate their relation to obesity pathogenesis., Methods: As a case-control study, we enrolled 83 non-obese persons as a control group with a BMI (18.5-24.9) and 83 obese persons as a patient group with a BMI > 30. All the study volunteers are subjected to anthropometric measurements, glucose, and lipid profile analysis by colorimetric methods. Serum trefoil factor 3 level was estimated by ELISA and leptin hormone was detected immunohistochemically in the blood using cell block technique., Results: ROC curve analysis for TFF3 showed a good relation with obesity with an AUC of 0.891 and a cut-off value of > 96 ng/ml. There was a significant positive correlation between TFF3 and fasting blood sugar, total cholesterol, and triglycerides. The logistic regression analysis showed that TFF3 is a good risk factor for obesity incidence [p = 0.008; OR = 1.117; (95 % CI): 1.029-1.213]. This was confirmed by multiple linear regression that gave an equation for the possibility of predicting BMI using several factors including TFF3 [BMI = 0.821 + 0.051 × TFF3 + 0.044 × FBS + 0.85 × TC]. The more surprising was the ability of the immunohistochemistry cell block technique to detect leptin antigens associated with an obese person blood not only adipose tissue or serum., Conclusion: Leptin hormone and TFF3 could be good indicators for obesity incidence. Further research with a larger sample size and in different populations could completely approve our results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: With aging, white adipose tissue (WAT) undergoes distribution change and browning inhibition, which could be attenuated by exercise. Adipokine chemerin exerts roles in the above changes of WAT, and our previous studies demonstrated the effect of decreased chemerin on exercise-induced improvement of glucose and lipid metabolism in high fat diet (HFD) feeding male mice, so this study is to clarify whether chemerin's effects on glucose and lipid metabolism are associated with the distribution and browning of WAT., Methods: After diet and exercise interventions, body weight and adipose tissue contents in different depots of male mice were weighed, body composition and energy metabolism parameters were determined by Echo MRI Body Composition Analyzer and metabolic cage, respectively. The levels of serum adiponectin and leptin were detected by ELISA, and the protein levels of PGC-1α, UCP1, adiponectin and leptin in WAT were measured by Western blot., Results: Chemerin knockout exacerbated HFD-induced weight gain, upregulated the increases of visceral and subcutaneous WAT (vWAT and sWAT, especial in sWAT), and inhibited WAT browning, but improved blood lipid. Exercise reduced the body weight and WAT distribution, increased sWAT browning and further improved blood lipid in aged HFD male mice, which were abrogated by chemerin knockout. Detrimental alterations of leptin, adiponectin and adiponectin/leptin ratio were discovered in the serum and WAT of aged HFD chemerin(-/-) mice; and exercise-induced beneficial changes in these adipokines were blocked by chemerin knockout., Conclusion: Chemerin influences blood lipid of aged male mice under HFD and exercise states through regulating the distribution and browning of WAT, which might be related to the changes of adiponectin, leptin and adiponectin/leptin ratio., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Increased adiposity is a significant risk factor for pancreatic cancer development. Multiple preclinical studies have documented that high-fat, high calorie diets, rich in omega-6 fatty acids (FA) accelerate pancreatic cancer development. However, the effect of a high-fat, low sucrose diet (HFD), on pancreatic carcinogenesis remains unclear. We evaluated the impact of a HFD on early-stage pancreatic carcinogenesis in the clinically relevant Kras LSL-G12D/+ ; Ptf1a Cre/+ (KC) genetically engineered mouse model, and characterized the role of the mesenteric adipose tissue (MAT). Cohorts of male and female KC mice were randomly assigned to a control diet (CD) or a HFD, matched for FA composition (9:1 of omega-6 FA: omega-3 FA), and fed their diets for 8 weeks. After 8 weeks on a HFD, KC mice had significantly higher body weight, fat mass, and serum leptin compared to CD-fed KC mice. Furthermore, a HFD accelerated pancreatic acinar-to-ductal metaplasia (ADM) and proliferation, associated with increased activation of ERK and STAT3, and macrophage infiltration in the pancreas, compared to CD-fed KC mice. Metabolomics analysis of the MAT revealed sex differences between diet groups. In females, a HFD altered metabolites related to FA (α-linolenic acid and linoleic acid) and amino acid metabolism (alanine, aspartate, glutamate). In males, a HFD significantly affected pathways related to alanine, aspartate, glutamate, linoleic acid, and the citric acid cycle. A HFD accelerates early pancreatic ADM through multifaceted mechanisms, including effects at the tumor and surrounding MAT. The sex-dependent changes in MAT metabolites could explain some of the sex differences in HFD-induced pancreatic ADM., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Obesity may promote kidney damage through hemodynamic and hormonal effects. We investigated the association between body mass index (BMI), total body fat (TBF) and chronic kidney disease (CKD) and whether hypertension, diabetes, leptin and adiponectin mediated these associations., Methods: In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study, 6671 participants (45-65 y) were included. We defined CKD as eGFR <60 ml/min/1.73 m 2 and/or moderately increased albuminuria. The percentage of mediation was calculated using general structural equation modeling, adjusted for potential confounding factors age, sex, smoking, ethnicity, physical activity and Dutch healthy diet index., Results: At baseline mean (SD) age was 56 (6), BMI 26.3 (4.4), 44% men, and 4% had CKD. Higher BMI and TBF were associated with 1.08 (95%CI 1.05; 1.11) and 1.05-fold (95%CI 1.02; 1.08) increased odds of CKD, respectively. As adiponectin was not associated with any of the outcomes, it was not studied further as a mediating factor. The association between BMI and CKD was 8.5% (95%CI 0.5; 16.5) mediated by diabetes and 22.3% (95%CI 7.5; 37.2) by hypertension. In addition, the association between TBF and CKD was 9.6% (95%CI -0.4; 19.6) mediated by diabetes and 22.4% (95%CI 4.2; 40.6) by hypertension. We could not confirm mediation by leptin in the association between BMI and CKD (35.6% [95%CI -18.8; 90.3]), nor between TBF and CKD (59.7% [95%CI -7.1; 126.6])., Conclusion: Our results suggest that the relations between BMI, TBF and CKD are in part mediated by diabetes and hypertension., (© 2024. The Author(s).)

Chronic stress lead to dysregulation of metabolic hormones, creating risk for obesity and type 2 diabetes. Based on previous work suggesting the potential for sexual activity to relieve psychological stress and reduce stress-related neuroendocrine activity, the present research explored sexual activity as a protective factor. We focused on chronic stress in the form of caregiving stress, comparing premenopausal mothers of a child with an autism spectrum disorder vs. a neurotypical child, in relation to metabolic hormones - insulin (and insulin resistance as assessed by HOMA), leptin, and ghrelin. Then, we explored the moderating role of sexual activity. Our results showed that high-stress mothers showed higher levels of insulin, insulin resistance, and lower levels of ghrelin compared to low-stress mothers. However, sexual activity modulated these associations such that among mothers who were sexually active (as coded from their daily diaries), no significant differences in these outcomes were observed between groups. This buffering effect of sexual activity was distinguishable from the buffering effect of physical activity and independent of global relationship satisfaction. Together, our findings provide novel evidence supporting the potential protective effects of sexual activity from chronic stress-related metabolic disease risk., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: The observed impacts of Garcinia cambogia (GC) on serum leptin indicate inconsistency. We performed a systematic review and meta-analysis on randomized controlled trials (RCTs) to evaluate the effectiveness of GC on leptin levels., Methods: A thorough literature search was carried out using different online databases, including Scopus, Web of Science, PubMed, and Google Scholar, until May 25, 2024. Using random effects, weighted mean differences (WMDs) and corresponding 95 % confidence intervals (CIs) were computed. Standard procedures were followed to account for publication bias, study quality, and statistical heterogeneity., Results: In this meta-analysis, a total of eight eligible trials with 330 participants were ultimately included. Quality assessment showed that half of the included trials were considered to have fair quality, while the other half were deemed to have poor quality. Our analysis, with no indication of publication bias, showed a significantly decreased effect of GC on leptin compared with the placebo (WMD: -5.01 ng/ml; 95 % CI: -9.22 to -0.80, p = 0.02). However, significant heterogeneity was detected between studies (I 2 =93.5 %, p < 0.001). The Hartung-Knapp adjustment did not affect our results. Subgroup analysis revealed that GC consumption represents the most effects in trials with sample size ≥ 50 (WMD: -3.63 ng/ml; 95 % CI [-5.51, -1.76], p < 0.001), and mean age of participants ≥ 30 years (WMD: -7.43 ng/ml; 95 % CI [-9.31, -5.56], p < 0.001)., Conclusions: The findings of the present study showed that leptin levels might decline following GC administration., Registration Number: CRD42023486370., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Perioperative neurocognitive disorders (NCD) are poorly characterized in terms of their risk factor profiles. Leptin and adiponectin are adipose-tissue-derived hormones with a role in inflammation and atherosclerosis whose function in perioperative NCD is unclear. Here, we used a cohort of older adults to examine the association of preoperative plasma concentrations of these biomarkers with the risk of perioperative NCD., Methods: Prospective analysis of 768 participants aged ≥ 65 years of the BioCog study. Blood was collected before surgery for measurement of plasma total and high-molecular-weight (hmw) adiponectin, leptin, and soluble leptin receptor (sOB-R). The free leptin index (FLI, leptin:sOB-R) was calculated. Postoperative delirium (POD) was assessed twice daily until postoperative day 7/discharge. Five hundred twenty-six patients (68.5%) returned for 3-month follow-up and provided data on postoperative cognitive dysfunction (POCD). POCD was defined as a decline on six neuropsychological tests that exceeded that of a nonsurgical control group. Logistic regression analyses examined the associations of each exposure with POD and POCD risk, in separate models adjusted for age, sex, fasting, surgery type, and body mass index (BMI)., Results: Of 768 patients, 152 (19.8%) developed POD. Of 526 attendants of the follow-up, 54 (10.3%) had developed POCD. Leptin, sOB-R, and total and hmw adiponectin were each not associated with POD. For POCD, we observed reduced risk in patients in FLI quartile 4 compared with quartile 1 (odds ratio, 0.26; 95% CI 0.08, 0.89). Sensitivity analyses for the outcome POD revealed statistically significant interaction terms of sOB-R and total adiponectin with obesity (BMI≥30kg/m 2 versus BMI<30kg/m 2 ). For the outcome POCD, a higher sOB-R was associated with an increased risk in the obese subgroup (odds ratio, 4.00; 95% CI 1.01, 15.86)., Conclusions: We did not find consistent evidence for the role of leptin, its receptor, and total and hmw adiponectin in POD and POCD risk. Future research should be used to support or refute our findings and to fully characterize any differences in the associations of these hormones with POD/POCD between obese and nonobese individuals., Competing Interests: DISCLOSURES This work was supported by theEuropean Union, Seventh Framework Programme(FP7/2007‐2013), under grant agreement no. HEALTH‐F2‐2014‐602461 BioCog (Biomarker Development for Postoperative Cognitive Impairment in the Elderly):www.biocog.eu. GW is coordinator of the BioCog consortium and is chief executive of the company Pharmaimage Biomarker Solutions GmbH (http://www.pi-pharmaimage.com). Among other academic and private partners, the company is a partner of the BioCog study. CD, AS, and TP are project leaders in BioCog. IF, JJ, AS, CS, and TP declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

To explore the effects of Du Meridian moxibustion combined with ear acupuncture on clinical symptoms and serum neurotransmitters in patients with coronary heart disease and insomnia. This study is a retrospective study. From June 2021 to May 2023, 116 patients with coronary heart disease and insomnia treated at our hospital were selected as subjects. They were divided into 2 groups according to the treatment. The control group received treatment with alprazolam, while the experimental group received Du Meridian moxibustion combined with ear acupuncture in addition to alprazolam treatment. The efficacy of the 2 groups was compared, and the levels of cardiac function indicators, serum melatonin, leptin, and neurotransmitters were measured. The total effectiveness rate in the experimental group was 93.10% (with a cure rate of 36.21%, a significant improvement rate of 41.38%, and an effective rate of 15.52%), which was significantly higher than the 79.31% in the control group (with a cure rate of 24.14%, a significant improvement rate of 32.76%, and an effective rate of 22.41%) (P < .05). Both groups exhibited an increase in left ventricular ejection fraction, stroke volume, and cardiac output after treatment compared to before treatment. Additionally, left ventricular end-systolic diameter decreased after treatment compared to before treatment, but the cardiac function was compared between the 2 groups after treatment (P > .05). In both groups, serum melatonin and serotonin (5-HT) levels increased after treatment compared to before treatment, while serum leptin, dopamine, and glutamate levels decreased after treatment compared to before treatment. Furthermore, the experimental group had higher serum melatonin, 5-HT, and gamma-aminobutyric acid levels compared to the control group, and lower serum leptin, dopamine, and glutamate levels compared to the control group (P < .05). The serum traditional Chinese medicine syndrome score and Pittsburgh sleep quality index score of the 2 groups decreased after treatment, and the experimental group was lower than the conventional group (P < .05). The combination of Du Meridian acupuncture with ear acupuncture in the treatment of insomnia in coronary heart disease can regulate the expression of serum melatonin, leptin, and neurotransmitters, alleviate symptoms, and improve therapeutic efficacy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: This study aims to compare the cognitive function of women with T1DM during and after pregnancy, as well as one year post-delivery. Additionally, it aims to investigate the impacts of leptin and body mass index on cognitive function., Methods: A prospective longitudinal cohort study was conducted involving 64 pregnant women with T1DM. Cognitive function was assessed using a cognitive assessment battery during the first trimester, immediately after delivery, and one year postpartum for the final assessment. This program evaluates a wide range of cognitive abilities and provides a comprehensive cognitive well-being score (high-moderate-low), identifying strengths and weaknesses in reasoning, memory, attention, coordination, and perception., Results: The average age of the participants was 30.9 years, with a mean diabetes duration of 14.9 years. Pregnant women with a BMI of 30 kg/m 2 or higher faced an increased risk of reduced cognitive function, memory, and reasoning. Additionally, mothers with lower overall cognitive function and memory levels had significantly higher concentrations of leptin in their blood., Conclusions: Cognitive functions-particularly reasoning and attention-are adversely affected in women with T1DM during pregnancy and shortly after delivery. Elevated BMI and leptin levels can be linked to worse cognitive outcomes in this population.

Biochemical recurrence is a process that progresses to castration-resistant prostate cancer (CRPC) and prediction of biochemical recurrence is useful in determining early therapeutic intervention and disease treatment. Prostate cancer is surrounded by adipose tissue, which secretes adipokines, affecting cancer progression. This study aimed to investigate the correlation between blood adipokines and CRPC biochemical recurrence. We retrospectively analyzed the clinical data, including preoperative serum adipokine levels, of 99 patients with pT3a pN0 prostate cancer who underwent proctectomy between 2011 and 2019. The primary outcome was biochemical recurrence (prostate-specific antigen: PSA > 0.2). We identified 65 non-recurrences and 34 biochemical recurrences (one progressed to CRPC). The initial PSA level was significantly higher ( p = 0.006), but serum adiponectin ( p = 0.328) and leptin ( p = 0.647) levels and their ratio ( p = 0.323) were not significantly different in the biochemical recurrence group compared with the non-recurrence group. In contrast, significantly more biochemical recurrences were observed in the group with adiponectin < 6 μg/mL and Leptin < 4 ng/mL ( p = 0.046), initial PSA > 15 ng/mL, clinical Gleason pattern ≥ 4, and positive resection margin. A significant difference was also observed in the multivariate analysis (hazard ratio: 4.04, 95% confidence interval: 1.21-13.5, p = 0.0232). Thus, low preoperative serum adiponectin and high leptin levels were significantly associated with biochemical recurrence in adipose tissue-invasive prostate cancer, suggesting that they may be useful predictors of biochemical recurrence. Further studies with larger cases are needed to increase the validity of this study.

Human milk (HM) composition, including metabolic hormones and lipids, is influenced by various factors, including lactation stage and, potentially, infant sex, which may affect infant body composition (BC) development. We aimed to: (a) characterize the longitudinal concentration and intake profiles of HM leptin, adiponectin, insulin, and total lipids; (b) determine if their concentrations and intakes differ by infant sex; and (c) explore the intakes relationships with the development of infant BC. Milk samples ( n = 501) were collected from 82 mother-infant dyads during the first 6 months postpartum. Infant 24 h HM intake was measured, and the average cumulative HM component intakes were calculated. The statistical analysis used linear mixed modeling. Intakes of HM leptin, adiponectin, insulin, and total lipids increased to 1 month postpartum and then remained stable. HM intake and total lipids intake but not hormone intakes were positively associated with infant BC (fat-free mass, fat-free mass index, fat mass, fat mass index, percentage fat mass, and fat mass to fat-free mass ratio). HM component concentrations and intakes did not differ by sex. These findings advance our understanding of the temporal nature of HM components, emphasizing the role of infant 24 h HM and total lipids intake in development of infant lean and adipose tissue.

Context: Studies have indicated a link between leptin, Alzheimer disease (AD), and Parkinson disease (PD). However, the causal relationship among them remains not well established due to confounders and reverse causation., Objective: This Mendelian randomization (MR) study was performed to evaluate the impact and potential mechanism of leptin and its soluble receptor on AD and PD., Methods: Utilizing genome-wide association studies summary-level data, a comprehensive MR was conducted to assess the causal effect of leptin and soluble leptin receptor (sLEPR) on AD and PD. Additionally, we also explored the role of body mass index (BMI) and insulin sensitivity index (ISI) in using the multivariable MR. The primary analysis was performed using the inverse variance-weighted method., Results: Pooled estimates showed that genetically proxied higher leptin levels was significantly associated with a decreased risk of AD (OR 0.838, 95% CI 0.741-0.948, P = .005), but not PD. In contrast, no significant associations were observed between sLEPR levels, AD, and PD. Moreover, the effect of leptin on AD was attenuated to null after adjustment of ISI (OR 0.879, 95% CI 0.758-1.018, P = .086), but not BMI. There was no causal impact of AD and PD on circulating levels of leptin and sLEPR, indicating the absence of reverse causation. Sensitivity analyses confirmed the robustness of these associations, with no obvious pleiotropy and heterogeneity., Conclusion: The study offers evidence supporting a potential protective effect of leptin in AD, but not PD, via the enhancement of insulin sensitivity. Our findings underscore the distinct roles of leptin in AD and PD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The aim of the study was to evaluate the diagnostic and prognostic significance of leptin receptor isoforms in adrenal tumors. In a single-center study, 96 patients (19 with adrenal cortical carcinoma and 77 with benign tumors) underwent an adrenalectomy. A total of 14 unaffected adrenal gland tissues from kidney donors were used as controls. Fasting blood samples were collected for laboratory tests, and mRNA expressions of leptin receptor isoforms were assessed by RT-qPCR. The study analyzed correlations between mRNA expressions and clinical data and measured NCI-H295R cell proliferation via a real-time cell analyzer. All adrenal lesions expressed leptin receptor isoforms. Significantly lower LepR1 expression was observed in carcinoma tissues than in adenomas and controls ( p = 0.016). Expressions of LepR3&LepR6 were correlated with overall survival ( p = 0.036), while LepR2&LepR4 and LepR5 expressions were inversely related to morning serum cortisol levels ( p = 0.041). Leptin reduced NCI-H295R cell proliferation ( p < 0.0001). The study highlights the diagnostic and prognostic significance of leptin receptor isoforms in adrenal tumors. Specifically, LepR1 may serve as a diagnostic marker for carcinomas, while LepR3&LepR6 have potential use as prognostic markers.

Objective. Genetic factors substantially contribute to the development and duration of arterial hypertension. The study of the A1166C polymorphism of the angiotensin II type 1 receptor gene ( AGTR1 ) in arterial hypertension is an auspicious area for assessing the relationship between heredity, hypertension development, and adipokines, but it still remains debatable. The purpose of the current study was to investigate serum adipokines levels depending on the AGTR1 A1166C polymorphism. Methods. A total of 86 patients with arterial hypertension were examined, who underwent the evaluation of the allelic A1166C polymorphism of AGTR1 by polymerase chain reaction with electrophoretic detection and determination of serum adipokines levels using enzyme-linked immunosorbent assay. Results. In the group of patients with arterial hypertension, a significant increase in serum adipokines (resistin, adiponectin, and leptin) levels was found against the background of a decrease in the antianorexic hormone ghrelin with a predominance of CC genotype carriers compared with AA genotype carriers of the AGTR1 . A statistically significant decrease in ghrelin and an increase in serum adipokines (resistin, adiponectin, and leptin) in CC genotype carriers compared with AA genotype carriers of the AGTR1 were found suggesting that CC genotype carriers may be predictors of the development of arterial hypertension in our patients. Conclusions. Statistically significant decrease in ghrelin and increase in serum adipokines (resistin, adiponectin, and leptin) were found in CC genotype carriers compared with AA genotype carriers of the AGTR1 , which suggests that carriers of the CC genotype are predictors of the arterial hypertension development in our patients., (© 2024 Svitlana Pidruchna et al., published by Sciendo.)

Introduction: Children and young adults with congenital adrenal hyperplasia (CAH) are at increased risk of obesity and insulin resistance. There is evidence that children with CAH have increased visceral adiposity, which has been linked to metabolic syndrome and cardiovascular disease (CVD). The adipokine adiponectin has been shown to correlate with reduced metabolic risk, whereas the adipokines visfatin and leptin have been linked to visceral fat and adipocyte inflammation and can serve as biomarkers of increased metabolic risk. Few studies to date have characterized adipokine levels in children and young adults with congenital adrenal hyperplasia. We sought to investigate the relationship between adiponectin, leptin and visfatin levels to metabolic risk factors and androgen levels in children and young adults with CAH., Methods: Fasting blood was obtained for visfatin, leptin, adiponectin, glucose, insulin, CRP, lipid panel, total cholesterol (TC), triglycerides (TG) and HbA1c, as well as standard laboratory tests to assess adrenal control, from children with CAH due to 21-hydroxylase deficiency. HOMA-IR was calculated based on fasting glucose and insulin. Anthropomorphic measurements of BMI and waist-to-hip ratio were also obtained., Results: Adiponectin and androstenedione were inversely correlated (R = -0.57, p =0.016). There was a positive correlation between leptin and BMI percentile (R = 0.63, p <0.001) as well as leptin and HOMA-IR (R = 0.63, p <0.01). Glucocorticoid dose had a positive correlation with HOMA-IR (R=0.56, p = 0.021). Visfatin was inversely correlated with HDL cholesterol (R = -0.54, p = 0.026) and total cholesterol (R = -0.49, p <0.05). Overweight children and young adults had a significantly higher leptin (p = 0.02) and HOMA-IR (p=0.001) than non-overweight children and young adults., Conclusion: The inverse relationship between adiponectin and androstenedione suggests that better CAH control can reduce the risk of insulin resistance and metabolic syndrome. However, a high glucocorticoid dose appears to increase the risk of insulin resistance, underscoring the delicate balance required when treating CAH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AK declared a past collaboration with the author OL to the handling editor., (Copyright © 2024 Apsan, Lekarev, Thomas, Zhu, Cohan and Lin-Su.)

Nonalcoholic fatty liver disease (NAFLD) affects over a third of the US population and 25% globally, with current treatments proving ineffective. This study investigates whether manipulating brown adipose tissue (BAT) and beige fat activity by housing C57BL/6J mice at thermoneutral (27 °C) or standard temperatures (22 °C) impacts NAFLD development. Male mice were fed either a chow diet (CHD) or a "fast food" diet (FFD) for 10 weeks. Mice at 27 °C had reduced food intake but increased body weight and plasma leptin levels. FFD-fed mice at 27 °C had greater liver weight (2.6 vs. 1.8 g), triglyceride content (7.6 vs. 3.9 mg/g), and hepatic steatosis compared to those at 22 °C. Gene expression of fatty acid synthase, sterol regulatory element-binding protein 1, and fatty acid translocase CD36 was elevated in FFD-fed mice at 27 °C, but not in CHD-fed mice. Thermoneutral housing also reduced expression of thermogenic markers in BAT and inguinal white adipose tissue (WAT) and caused BAT whitening. In conclusion, thermoneutrality inhibits thermogenic markers and exacerbates NAFLD. Activating BAT or promoting WAT browning via cold exposure or other stimuli may offer a strategy for managing NAFLD.

Background: Individuals of South Asian origin have a greater risk of cardiovascular disease after gestational diabetes mellitus (GDM) than European individuals. B-type natriuretic peptide (BNP) and the amino-terminal fragment of its prohormone (NT-proBNP) are commonly used for heart failure screening and diagnosis, but biologically BNP exerts several beneficial cardiovascular effects primarily by counteracting the renin-angiotensin-aldosterone-system. We asked whether ethnic differences in circulating NT-proBNP levels could be explained by the differences in cardiometabolic and inflammatory risk markers?, Methods: We examined 162 South Asian and 107 Nordic women in Norway 1-3 years after GDM with a clinical examination, fasting blood samples and an oral glucose tolerance test. We measured the levels of NT-proBNP, high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), leptin, adiponectin and markers of insulin sensitivity, such as the Matsuda insulin sensitivity index (ISI). Finally, we tried to identify which independent covariate best mediated the ethnic differences in NT-proBNP., Results: The mean (SD) age was 35.3 (4.5) years, BMI 29.1 (6.0) kg/m 2 , waist-height ratio 0.60 (0.08) and 164 women (61%) had prediabetes/diabetes. Notably, South Asian women had lower levels of NT-proBNP than Nordic women in both the normoglycemic and prediabetes/diabetes groups (median (IQR) 26  (15-38)  vs. 42 (22-66) ng/L, p < 0.001). Higher NT-proBNP levels were associated with greater insulin sensitivity in both South Asian and Nordic women (p = 0.005 and p < 0.001). South Asian women had higher levels of hsCRP (median (IQR) 2.2 (1.1-4.4) vs. 1.2 (0.3-4.2) mg/L), IL-6 (2.3 (1.5-3.2) vs. 1.5 (1.5-2.5) pg/mL), leptin (1647 (1176-2480) vs. 1223 (876-2313) pmol/L), and lower adiponectin levels (7.2 (5.3-9.3) vs. 10.0 (7.2-13.5) mg/L) and Matsuda ISI (2.4 (1.7-3.7) vs. 4.2 (2.9-6.1), p all <0.01) than Nordic women. Even after adjusting for these differences, higher NT-proBNP levels remained associated with insulin sensitivity (22% higher NT-proBNP per SD Matsuda ISI, p = 0.015). Insulin sensitivity and adiponectin mediated 53% and 41% of the ethnic difference in NT-proBNP., Conclusions: NT-proBNP levels are lower in South Asian than in Nordic women after GDM. Lower NT-proBNP levels correlate with impaired insulin sensitivity. Lower NT-proBNP levels in South Asian women could, therefore, be attributed to impaired insulin sensitivity rather than total body fat., (© 2024. The Author(s).)

Objective: To investigate the possible association of periorbital melanosis (POM) with insulin resistance (IR) and vitamin D serum levels., Methods: In this pilot, case-control study, we included 100 adult patients with POM and 100 age- and sex-matched healthy control subjects. Vitamin D levels and IR indices (i.e., homeostatic model assessment-insulin resistance [HOMA-IR], triglycerides/high-density lipoprotein cholesterol (TG/HDL-c) ratio, adiponectin/leptin (A/L) ratio) were compared between cases and controls., Results: Compared with controls, POM cases had significantly higher values of HOMA-IR and TG/HDL-c ratio, and significantly lower values of A/L and vitamin D. HOMA-IR and TG/HDL-c ratio were statistically significantly positively correlated with POM severity while Vitamin D and A/L ratio were statistically significantly negatively correlated., Conclusion: POM was associated with indices of IR and vitamin D deficiency. However, the exact causal link among POM, IR, and vitamin D needs to be established. However, the results of this pilot study suggest that POM may have potential as a cutaneous non-invasive marker of these metabolic disorders which would assist in detecting and treating them at an early stage., Competing Interests: Declaration of conflicting interestsThe authors declare there are no conflicts of interest.

Introduction: Neuropeptide Y is a neurotransmitter in the nervous system and belongs to the orexigenic system that increases appetite. Its excessive secretion leads to obesity. Leptin is a pro-inflammatory adipokine (produced in adipose tissue) induced in obesity and may mediate increased antitumor immunity in obesity (including the promotion of M1 macrophages). Leptin and neuropeptide Y gene polymorphisms, causing increased leptin levels and the occurrence of obesity, and lipid profile disorders, may increase the effectiveness of immunotherapy., Materials and Methods: In 121 patients with advanced NSCLC without mutations in the EGFR gene and rearrangements of the ALK and ROS1 genes, undergoing immunotherapy (1st and 2nd line of treatment) or chemoimmunotherapy (1st line of treatment), we assessed BMI, lipid profile, PD-L1 expression on cancer cells using the immunohistochemical method (clone SP263 antibody), leptin concentration in blood serum by ELISA, polymorphisms in the promoter region of the genes for leptin (LEP) and neuropeptide Y (NPY) by real-time PCR., Results: Leptin concentration was significantly higher in obese patients than in patients with normal or low weight (p = 0.00003) and in patients with disease stabilization compared to patients with progression observed during immunotherapy (p = 0.012). Disease control occurred significantly more often in patients with the GA or AA genotype than patients with the GG genotype in the rs779039 polymorphism of the LEP gene. The median PFS in the entire study group was five months (95% CI: 3-5.5), and the median OS was 12 months (95% CI: 8-16). Median PFS was highest in patients with TPS ≥ 50% (6.5 months) and in obese patients (6.6 months). Obese patients also had a slightly longer median OS compared to other patients (23.8 vs. 13 months). The multivariate Cox logistic regression test showed that the only factor reducing the risk of progression was TPS ≥ 50% (HR = 0.6068, 95% CI: 0.4001-0.9204, p = 0, 0187), and the only factor reducing the risk of death was high leptin concentration (HR = 0.6743, 95% CI: 0.4243-1.0715, p = 0.0953)., Conclusion: Assessment of nutritional status, serum leptin concentration and polymorphisms in the LEP gene may be of additional importance in predicting the effectiveness of immunotherapy and chemoimmunotherapy in patients with advanced NSCLC., (© 2024. The Author(s).)

Objective: The aim of this study was to evaluate the relationship between levels of leptin, growth hormone (GH), and ghrelin in the bloodstream and fibromyalgia., Methods: We conducted a meta-analysis to compare the serum/plasma levels of leptin, GH, and ghrelin in individuals with fibromyalgia, as compared to healthy controls. The analysis included sixteen articles, which provided data from 697 fibromyalgia patients and 560 controls., Results: The meta-analysis found that there was no significant difference in leptin levels between fibromyalgia patients and controls overall (SMD = 0.324, 95% CI = -0.264 to 0.913, P = 0.281). However, when subgroup analysis was done based on geographically different populations, it showed a positive association between high leptin levels and fibromyalgia in European populations (SMD = 1.131, 95% CI = 0.197 to 2.064, P = 0.018), while no significant association was found in Latin American populations (SMD = -0.160, 95% CI = -0.847 to 0.528, P = 0.649). As for GH levels, there was no significant difference between fibromyalgia patients and controls overall (SMD = -0.903, 95% CI = -2.036 to 0.231, P = 0.119). However, when subgroup analysis was done based on geographically different populations, it revealed a significant decrease in GH levels in European populations with fibromyalgia (SMD = -2.341, 95% CI = -3.664 to -1.017, P = 0.001), while no significant association was found in North American populations. Lastly, the analysis of ghrelin levels showed no significant association with fibromyalgia overall (SMD = -0.661, 95% CI = -1.382 to 0.059, P = 0.072)., Conclusion: This meta-analysis shows that patients with fibromyalgia in Europeans have significantly higher levels of circulating leptin and GH. However, no significant association was found between ghrelin levels and fibromyalgia., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: A wealth of evidence underscores the bioactive properties of nutraceuticals and functional foods in addressing oxyinflammatory-based diseases with implications at both peripheral and central levels. Opuntia ficus-indica (OFI) is well-documented for its health-promoting attributes, though its fruit (OFIF) remains relatively understudied. Not only poses Metabolic Syndrome (MetS) cardiometabolic risks but also contributes significantly to cognitive impairment, especially in crucial brain areas such as hippocampus and hypothalamus., Methods: Following 8 weeks of HFD to induce MetS, rats received OFIF oral supplementation for 4 weeks to evaluate cognitive and affective modifications using behavioural paradigms, i.e. open field, burrowing, white-dark box, novelty-suppressed feeding, and object recognition tests. Our investigation extended to biochemical evaluations of lipid homeostasis, central and peripheral oxidative stress and neurotrophic pathways, correlating these measures together with circulating leptin levels., Results: Our data revealed that OFIF modulation of leptin positively correlates with systemic and brain oxidative stress, with markers of increased anxiety-like behaviour and impaired lipid homeostasis. On the other hand, leptin levels reduced by OFIF are associated with improved antioxidant barriers, declarative memory and neurotrophic signalling., Discussion: This study underscores OFIF neuroactive potential in the context of MetS-associated cognitive impairment, offering insights into its mechanisms and implications for future therapeutic strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

This study aimed to investigate the levels of serum, gingival crevicular fluid (GCF), and salivary adipokines and their possible relationship with periodontitis and obesity. An electronic search was conducted in the following databases: PubMed/ Medline, Scopus, and EBSCOhost through February 2023. Two independent reviewers screened the titles, abstracts, and full text of all the studies. Studies comparing the levels of adipokines in GCF, serum, and/or saliva in subjects with obesity and periodontitis (group 1), subjects with normal weight and periodontitis (group 2), and subjects with obesity and gingival health (group 3) were included. Meta-analyses and meta-regression were performed on the data from included studies. Seventeen studies with study participants ranging from 30 to 120 were included with subjects in each group ranging from 10 to 40. There was a significant increase in levels of serum TNF-α, leptin, IL-6, and CRP between groups 1 and 2 (p < .05). In GCF, TNF-α and resistin levels were significantly higher (p < .05) in Group 1 vs. 2. Serum level of leptin was higher for group 1 vs. 3 (p < .05). Meta-regression analysis revealed that the obesity definition (body mass index (BMI) cut-off value >25 or >30) was significant for serum resistin (p < .05) and GCF resistin (p < .05) between group 1 and 2. The current analysis indicates that both periodontitis and obesity can modulate the pro-inflammatory cytokines at systemic and local levels. This bidirectional interaction of periodontitis and obesity via the inflammation pathway seems likely plausible. Further studies are required to elucidate this mechanism in more detail., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Rheumatoid arthritis can be classified according to ACPA and RF status. ACPA status may be associated with other pathophysiological differences, e.g., the cytokines driving inflammation. Obesity influences the course of RA, likely involving leptin; the exact mechanisms are not completely understood. This study investigates BMI influence on RA cytokine profiles and the possibility of predicting ACPA status and disease activity measured by Power-Doppler sonography (PDS)., Methods: Patients were examined using a multi-biomarker disease assay and PDS examination of wrists and MCP and PIP joints and stratified according to ACPA status and BMI, using prediction precision to determine BMI cutoff. Analysis was performed using elastic net regularization of logistic and multiple regression. We then attempted to predict ACPA status/PDS activity based on a bootstrap approach., Results: A total of 120 measurements from 95 patients were performed. ACPA status prediction peaked at BMI 26 kg/m 2 , with AUC 0.82. PDS activity prediction had a mean average error of < 1.6 PDS points for all groups. In obese patients, cytokine profiles appear to align in ACPA-positive and -negative patients, with leptin playing a greater role in predicting PDS activity, but with some remaining differences., Conclusion: When stratified according to BMI, cytokine patterns can predict ACPA status and PDS activity in RA with a high degree of precision. This indicates that studies into the pathophysiology of RA should take BMI into account, to differentiate between disease- and obesity-associated phenomena. The underlying pathological processes of ACPA-negative and -positive RA appear different. Multi-cytokine evaluations may provide a deeper understanding of disease processes. Key Points • A multi-cytokine approach combined with ultrasonography and modern mathematical methods can contribute to a deeper understanding of the relationship between systemic and joint inflammation. • BMI influences cytokine profiles in rheumatoid arthritis and appears to "override" disease-specific processes. • Using cytokines only, and adjusting for BMI, it is possible to predict the ACPA status and joint inflammation with considerable precision., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

The objective of the study was to identify different phenotypes of overweight in women with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) based on body mass index (BMI) and serum leptin levels, as well as to determine the frequencies of various metabolic disorders, hypertension, and cardiovascular complications (CVCs) in individual phenotypes. The study included 50 women with RA and 46 with SLE aged 18 to 65 years without a history of diabetes and fasting hyperglycemia. In all patients, the concentration of leptin was determined by ELISA, the concentration of insulin was determined by electrochemiluminescence analysis, and the HOMA-IR index was calculated. Hyperleptinemia was diagnosed at leptin concentrations > 11.1 ng/mL; insulin resistance (IR), at HOMA-IR values ≥ 2.77. Three main phenotypes of overweight were distinguished: "classic" (BMI ≥ 25 kg/m 2 + hyperleptinemia), "healthy" (BMI ≥ 25 kg/m 2 , without hyperleptinemia), "hidden" or "latent" (BMI < 25 kg/m 2 + hyperleptinemia), as well as "normal weight" (BMI < 25 kg/m 2 , without hyperleptinemia). Patients with RA and SLE were similar in age (p = 0.4), disease duration (p = 0.2) and BMI (p = 0.5). Hyperleptinemia was found in 46% of women with RA and in 74% of women with SLE (p = 0.005), and IR was found in 10 and 22% of patients, respectively (p = 0.2). The "classic" phenotype of overweight was diagnosed in 30%, "healthy" in 8%, and "hidden" in 16% of cases with RA and in 44%, 0%, and 30% of cases with SLE, respectively. IR was found in 3% and hypertension in 6% of patients with "normal weight." With the "classic" phenotype, IR (29%) and hypertension (66%) were more common than with "normal weight" (p < 0.01 in all cases); with the "hidden" phenotype, significant differences were obtained only in hypertension frequency (45%; p = 0.0012), but not IR (18%). Three out of four women with a history of cardiovascular complications suffered from "classic" overweight, and one patient had a "normal weight." In women with SLE up to 65 years of age, the frequency of hyperleptinemia, but not IR, is higher than in patients with RA. In both diseases, the "classic" overweight phenotype is most common. In RA, a "hidden" phenotype was detected less often than in SLE, at the same time, a "healthy" phenotype is not characteristic of SLE. The frequency of metabolic disorders and hypertension is low with the "normal weight" and "healthy" phenotype, high with the "classic" phenotype, and intermediate with the "hidden" phenotype., (© 2024. Pleiades Publishing, Ltd.)

Background: The association between the adiponectin-to-leptin ratio (A/L ratio) and the risk of incident chronic kidney disease (CKD) is poorly understood. This study aimed to investigate the association between A/L ratio and the risk of incident CKD and to examine whether such a relationship varied according to sex and body composition., Methods: In this prospective community-based cohort, participants with normal kidney function were analysed (N = 5192). The association between the A/L ratio at baseline and the risk of incident CKD, defined as two or more occasions with an estimated glomerular filtration rate of <60 mL/min/m 2 or proteinuria of ≥1+ on a dipstick test during the follow-up period, was evaluated using multivariable Cox proportional hazards analyses. Subgroup analyses were conducted based on sex, body mass index (BMI) and the presence of sarcopenia., Results: The participants' mean age was 57.2 ± 8.3 years, and 53.2% were women. The A/L ratio was higher in men compared with women (1.5 [0.8-3.2] and 0.5 [0.3-0.9] μg/ng, P < 0.001). During a median follow-up of 9.8 [9.5-10.0] years, 417 incident CKD events occurred (8.7 per 1000 person-years). Men in the highest quartile of A/L ratio had a lower risk of incident CKD (adjusted hazard ratio [aHR], 0.57; 95% confidence interval [CI], 0.33-0.99) than those in the lowest quartile. Additionally, a 1.0 increase in A/L ratio was associated with a 12% decreased risk of incident CKD in men (aHR, 0.88; 95% CI, 0.80-0.97). However, no significant association was observed in women. In subgroup analysis stratified by BMI and the presence of sarcopenia, the association between a high A/L ratio and a reduced risk of incident CKD was consistent in men with a BMI < 23.0 kg/m 2 and those with sarcopenia. However, no significant association was observed between men with a BMI ≥ 23.0 kg/m 2 and those without sarcopenia., Conclusions: A high A/L ratio is an independent marker of a reduced risk of incident CKD in men, especially in those with a BMI < 23.0 kg/m 2 and sarcopenia., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

We evaluated glycemia and triglyceride, hepatic, muscular, and renal damage markers, redox profile, and leptin and ghrelin hormone levels in COVID-19 patients. We also conducted statistical analysis to verify the potential of biomarkers to predict poor prognosis and the correlation between them in severe cases. We assessed glycemia and the levels of triglycerides, hepatic, muscular, and renal markers in automatized biochemical analyzer. The leptin and ghrelin hormones were assessed by the ELISA assay. Severe cases presented high glycemia and triglyceride levels. Hepatic, muscular, and renal biomarkers were altered in severe patients. Oxidative stress status was found in severe COVID-19 patients. Severe cases also had increased levels of leptin. The ROC curves indicated many biomarkers as poor prognosis predictors in severe cases. The Spearman analysis showed that biomarkers correlate between themselves. Patients with COVID-19 showed significant dysregulation in the levels of several peripheral biomarkers. We bring to light that a robust panel of peripheral biomarkers and hormones predict poor prognosis in severe cases of COVID-19 and biomarkers correlate with each other. Early monitoring of these biomarkers may lead to appropriate clinical interventions in patients infected by SARS-CoV2., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Increased adiposity during pregnancy may be related to offspring risk for mental health disorders, although the biological mechanisms are poorly understood. One promising hypothesis is that factors secreted from adipocytes such as leptin and adiponectin may explain this association. The current study examined whether pregnancy or umbilical cord blood concentrations of leptin and/or adiponectin a) predict elevated infant negative affect at 6 months (an early life marker of risk for psychopathology); and b) help explain the association between pregnancy adiposity and increased infant negative affect., Methods: Data came from a prospective cohort (N = 305) of pregnant individuals and their offspring. Second trimester adiposity was assessed using air displacement plethysmography. Concentrations of leptin and adiponectin were measured in second trimester plasma and umbilical cord plasma. Infant negative affect was assessed by standardized observation at 6 months. Second trimester inflammation was assessed using a comprehensive panel of cytokines., Results: Lower second trimester adiponectin was associated with elevated infant negative affect, and mediated the effect of pregnancy adiposity on infant negative affect. This association was independent of the effect of second trimester inflammation. Umbilical cord leptin also predicted higher infant negative affect and mediated the association between pregnancy adiposity and infant negative affect., Conclusions: This is the first study to link pregnancy adiponectin or cord blood leptin to infant markers of risk for psychopathology, and the first to demonstrate that these adipokines mediate the association between pregnancy adiposity and offspring behavioral outcomes, suggesting novel markers of risk and potential mechanisms of effect., Competing Interests: Declaration of competing interest We have no known conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Eating frequency (EF) focuses on the total number of eating occasions per day and may influence metabolic health., Objectives: We sought to examine the effect of high compared with low EF on appetite regulation and inflammatory biomarkers among healthy adults., Methods: Data are from a randomized, crossover trial (the Frequency of Eating and Satiety Hormones study). Participants (n = 50) completed 2 isocaloric 21-d study periods of low EF (3 eating occasions/d) and high EF (6 eating occasions/d) in random order with a 14-d washout period in between. Participants were free-living and consumed their own food, using study-directed, structured meal plans with identical foods and total energy in both study periods. On days 1 and 21 of each EF period, fasting blood was collected during in-person clinic visits to assess plasma concentrations of ghrelin, leptin, adiponectin, and high-sensitivity C-reactive protein (hs-CRP). Linear mixed models with EF, diet sequence, and period as fixed effects and participant as random effect were used to estimate the intervention effect. Interaction effects between EF and body fat percentage were examined., Results: Among the 50 participants who completed the trial, 39 (78%) were women, 30 (60%) were Non-Hispanic White, and 40 (80%) had a body mass index of <25 kg/m 2 , and the mean age was 32.1 y. The differences between high and low EF in fasting ghrelin (geometric mean difference: 17.76 ng/mL; P = 0.60), leptin (geometric mean difference: 2.09 ng/mL; P = 0.14), adiponectin (geometric mean difference: 381.7 ng/mL; P = 0.32), and hs-CRP (geometric mean difference: -0.018 mg/dL; P = 0.08) were not statistically significant. No significant interaction was observed between EF and body fat percentage on appetite regulation and inflammatory biomarkers., Conclusions: No differences was observed in fasting ghrelin, leptin, adiponectin, and hs-CRP comparing high and low EF. Future studies are needed to understand the physiology of EF and appetite as they relate to metabolic health. This trial was registered at clinicaltrials.gov as NCT02392897., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Purpose: The differential diagnosis of lipodystrophy involves other disorders characterized by severe fat loss and may be sometimes challenging. Owing to the rarity of lipodystrophy, it is relevant to search for tools and assays that differentiate it from other diseases that may mimic it. We conducted a study on leptin and high molecular weight (HMW) adiponectin serum concentrations in a series of patients diagnosed with lipodystrophy and compared them with those found in anorexia nervosa, one of the illnesses that may be cause of a missed diagnosis of lipodystrophy., Methods: Leptin and HMW adiponectin serum concentrations were measured in six patients diagnosed with generalized lipodystrophy (GL), six with progeroid syndromes (PS), 13 with familial partial lipodystrophy type 1 (FPLD1, Kobberling syndrome), 10 with familial partial lipodystrophy type 2 (FPLD2, Dunnigan syndrome), 18 with acquired partial lipodystrophy (APL) and 12 affected by anorexia nervosa (AN). Measurements were compared to those obtained in 12 normal weight healthy subjects., Results: Serum leptin concentrations were reduced to a similar degree in GL, PS and AN, proportionally to the extent of fat loss. Serum concentrations of HMW adiponectin were found extremely low in patients with GL and PS, while comparable to normal weight subjects in patients with AN., Conclusion: Serum HMW adiponectin can be regarded as a useful tool to discriminate between generalized lipodystrophy syndromes (including PS) and AN., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Despite some reported benefits, there is a low quality of evidence for resistance training (RT) improving metabolic health of individuals with overweight or obesity. We evaluated the impact of RT on body composition, cardiorespiratory fitness (CRF) and physical performance, lipid-lipoprotein profile, inflammation, and glucose-insulin homeostasis in 51 postmenopausal women versus 29 controls matched for age, obesity, and physical activity. Exercised women were further subdivided for comparison of RT effects into those presenting metabolically healthy obesity (MHO) and those with metabolically unhealthy obesity (MUHO) classified according to Karelis and Rabasa-Lhoret or an approach based on adipose tissue secretory dysfunction using the plasma adiponectin(A)/leptin (L) ratio. Participants followed a 4-month weekly RT program targeting major muscle groups (3 × 10 repetitions at 80% one repetition maximum (1-RM)). Percent fat marginally decreased and lean body mass increased (0.01 <  p  < 0.05) while CRF and muscular strength improved in all women, after RT (effect size (ES): 0.11-1.21 (trivial to large effects), p ˂ 0.01). Fasting plasma triacylglycerol and high-density lipoprotein-cholesterol levels slightly increased and decreased, respectively, in participants with MHO using the A/L ratio approach (ES: -0.47 to 1.07 (small to large effects), p ˂ 0.05). Circulating interleukin-6 soluble receptor decreased in both groups and soluble tumor necrosis factor receptor-1/soluble tumor necrosis factor receptor-2 in women with MUHO only, irrespective of definition (ES: -0.42 to -0.84 (small to large effects), p ˂ 0.05). Glucose-insulin homeostasis was unchanged regardless of group or definition. RT improved physical performance and body composition but had a lesser impact on cardiometabolic risk in women with obesity, irrespective of their metabolic phenotype., Competing Interests: The authors declare that they have no conflict of interest related to the present study. AT receives funding from Johnson & Johnson, Medtronic, and GI Windows for research unrelated to the present study. AT also acted as consultant for Novo Nordisk, Bausch Health, and Biotwin. The authors alone are responsible for the contents and writing of the paper.

Obesity in adolescence is increasing in frequency and is associated with elevated proinflammatory cytokines and chronic pain in a sex-dependent manner. Dietary probiotics may mitigate these detrimental effects of obesity. Using a Long-Evans adolescent and adult rat model of overweight (high-fat diet (HFD) - 45% kcal from fat from weaning), we determined the effect of a single-strain dietary probiotic [ Lactiplantibacillus plantarum 299v (Lp299v) from weaning] on the theoretically increased neuropathic injury-induced pain phenotype and inflammatory cytokines. We found that although HFD increased fat mass, it did not markedly affect pain phenotype, particularly in adolescence, but there were subtle differences in pain in adult male versus female rats. The combination of HFD and Lp299v augmented the increase in leptin in adolescent females. There were many noninteracting main effects of age, diet, and probiotic on an array of cytokines and adipokines with adults being higher than adolescents, HFD higher than the control diet, and a decrease with probiotic compared with placebo. Of particular interest were the probiotic-induced increases in IL12p70 in female adolescents on an HFD. We conclude that a more striking pain phenotype could require a higher and longer duration caloric diet or a different etiology of pain. A major strength of our study was that a single-strain probiotic had a wide range of inhibiting effects on most proinflammatory cytokines. The positive effect of the probiotic on leptin in female adolescent rats is intriguing and worthy of exploration. NEW & NOTEWORTHY A single-strain probiotic (Lp299v) had a wide range of inhibiting effects on most proinflammatory cytokines (especially IL12p70) measured in this high-fat diet rat model of mild obesity. The positive effect of probiotic on leptin in female adolescent rats is intriguing and worthy of exploration.

It is possible that the reproductive strategy of the short-beaked echidna is related to seasonal changes in fat deposition and energy availability, regulated by seasonal changes in endocrine function. We predicted that circulating leptin levels would be directly proportional to adiposity during most of the year, but that a change in this relationship would occur during the pre-breeding season to allow increased fat deposition. To test this hypothesis, we made use of a captive colony of echidnas to describe and quantify changes in fat distribution and the adipostatic hormone leptin. First we assessed seasonal changes in circulating leptin levels, body mass and adiposity for three male and three female adult echidnas maintained on a standard diet. Second, we explored the relationship between circulating leptin levels and increased caloric intake for an additional five adult female echidnas that were provided with supplemented nutrition. Third we visualised fat distribution in male and female adult echidnas using magnetic resonance imaging (MRI) before and after the breeding season, to determine where fat is deposited in this species. For echidnas maintained on the standard diet, there were no seasonal changes in body mass, body fat or plasma leptin levels. However, female echidnas provided with supplemented nutrition had significantly elevated plasma leptin levels during the breeding season, compared to the pre-and post- breeding periods. MRI showed substantial subcutaneous fat depots extending dorso-laterally from the base of the skull to the base of the tail, in both sexes. Pre-breeding season, both sexes had considerable fat deposition in the pelvic/rump region, whilst the female echidna accumulated most fat in the abdominal region. This study shows that male and female echidnas accumulate body fat in the pelvic/rump and the abdominal regions, respectively and that circulating leptin may promote fattening in female echidnas during the breeding season by means of leptin resistance. However, further research is required to evaluate the precise relationship between seasonal changes in leptin and adiposity., (© 2024. The Author(s).)

Syrian hamsters are valuable models for studying lipid metabolism due to their sensitivity to dietary cholesterol, yet the precise impact of varying cholesterol levels has not been comprehensively assessed. This study examined the impact of varying dietary cholesterol levels on lipid metabolism in Syrian hamsters. Diets ranging from 0% to 1% cholesterol were administered to assess lipid profiles and oxidative stress markers. Key findings indicate specific cholesterol thresholds for inducing distinct lipid profiles: below 0.13% for normal lipids, 0.97% for elevated LDL-C, 0.43% for increased VLDL-C, and above 0.85% for heightened hepatic lipid accumulation. A cholesterol supplementation of 0.43% induced hypercholesterolemia without adverse liver effects or abnormal lipoprotein expression. Furthermore, cholesterol supplementation significantly increased liver weight, plasma total cholesterol, LDL-C, and VLDL-C levels while reducing the HDL-C/LDL-C ratio. Fecal cholesterol excretion increased, with stable bile acid levels. High cholesterol diets correlated with elevated plasma ALT activities, reduced hepatic lipid peroxidation, and altered leptin and CETP levels. These findings underscore Syrian hamsters as robust models for hyperlipidemia research, offering insights into experimental methodologies. The identified cholesterol thresholds facilitate precise lipid profile manipulation, enhancing the hamster's utility in lipid metabolism studies and potentially informing clinical approaches to managing lipid disorders.

Exercise training is a valuable tool for improving body weight and composition in overweight or obese adults, which leads to a negative energy balance. It is relevant to consider whether exercise can help people lose weight or prevent weight gain because any energy expended in exercise increases the severity of hunger and promotes food consumption. Over the past decade, the identification of the circulating peptide ghrelin, which alerts the brain to the body's nutritional state, has significantly expanded our understanding of this homeostatic mechanism that controls appetite and body weight. To shed more light on this issue, we decided to investigate the effects of resistance and endurance training on plasma ghrelin and leptin levels. In addition, we sought to understand the mechanisms by which acute and chronic exercise can regulate hunger. This review analyzes studies published in the last fifteen years that focused on changes suffered by ghrelin, leptin, or both after physical exercise in overweight or obese individuals. Most studies have shown a decrease in leptin levels and an increase in ghrelin levels in these cases. Exercise regimens that support weight maintenance need further investigation.

We recently indicated that four-week probiotic supplementation significantly reduced depression along with microbial and neural changes in people with depression. Here we further elucidated the biological modes of action underlying the beneficial clinical effects of probiotics by focusing on immune-inflammatory processes. The analysis included a total of N = 43 participants with depression, from which N = 19 received the probiotic supplement and N = 24 received a placebo over four weeks, in addition to treatment as usual. Blood and saliva were collected at baseline, at post-intervention (week 4) and follow-up (week 8) to assess immune-inflammatory markers (IL-1β, IL-6, CRP, MIF), gut-related hormones (ghrelin, leptin), and a stress marker (cortisol). Furthermore, transcriptomic analyses were conducted to identify differentially expressed genes. Finally, we analyzed the associations between probiotic-induced clinical and immune-inflammatory changes. We observed a significant group x time interaction for the gut hormone ghrelin, indicative of an increase in the probiotics group. Additionally, the increase in ghrelin was correlated with the decrease in depressive symptoms in the probiotics group. Transcriptomic analyses identified 51 up- and 57 down-regulated genes, which were involved in functional pathways related to enhanced immune activity. We identified a probiotic-dependent upregulation of the genes ELANE, DEFA4 and OLFM4 associated to immune activation and ghrelin concentration. These results underscore the potential of probiotic supplementation to produce biological meaningful changes in immune activation in patients with depression. Further large-scale mechanistic trials are warranted to validate and extend our understanding of immune-inflammatory measures as potential biomarkers for stratification and treatment response in depression. Trial Registration: www.clinicaltrials.gov , identifier: NCT02957591., (© 2024. The Author(s).)

Weight loss is often followed by weight regain. Characterizing endocrine alterations accompanying weight reduction and regain may disentangle the complex biology of weight-loss maintenance. Here, we profile energy-balance-regulating metabokines and sphingolipids in adults with obesity undergoing an initial low-calorie diet-induced weight loss and a subsequent weight-loss maintenance phase with exercise, glucagon-like peptide-1 (GLP-1) analog therapy, both combined, or placebo. We show that circulating growth differentiation factor 15 (GDF15) and C16:0-C18:0 ceramides transiently increase upon initial diet-induced weight loss. Conversely, circulating fibroblast growth factor 21 (FGF21) is downregulated following weight-loss maintenance with combined exercise and GLP-1 analog therapy, coinciding with increased adiponectin, decreased leptin, and overall decrements in ceramide and sphingosine-1-phosphate levels. Subgroup analyses reveal differential alterations in FGF21-adiponectin-leptin-sphingolipids between weight maintainers and regainers. Clinically, cardiometabolic health outcomes associate with selective metabokine-sphingolipid remodeling signatures. Collectively, our findings indicate distinct FGF21, GDF15, and ceramide responses to diverse phases of weight change and suggest that weight-loss maintenance involves alterations within the metabokine-sphingolipid axis., Competing Interests: Declaration of interests A family member of R.M.S. holds Novo Nordisk stocks. S.M. is on advisory boards of AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, and Sanofi Aventis; receives lecture fees from AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Novo Nordisk, and Sanofi Aventis; and is a research grant recipient from Novo Nordisk and Boehringer Ingelheim. J.J.H. is on the advisory board of Novo Nordisk. S.S.T. is a research grant recipient and receives lecture fees from Novo Nordisk., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Metabolic disorders pose significant challenges in transition dairy cows. Numerous parameters have been investigated in this context, and apelin has recently emerged as a potential metabolic indicator. Accordingly, this study aimed to assess the associations between this hormone and other metabolic parameters. Twenty-two adult Holstein-Friesian dairy cows, 21 days before their expected calving date, were selected for blood sampling and serum separation at four time points: 21 and 10 days before calving and 10 and 21 days after parturition. Serum concentrations of apelin, leptin, insulin, cortisol, T3, T4, non-esterified fatty acids, glucose, total protein, albumin, globulin, aspartate aminotransferase, alanine transaminase, triglycerides, cholesterol, high, low and very low-density lipoproteins, total, direct and indirect bilirubin were measured in these samples. Surrogate indices for insulin resistance, body condition score, and milk production were also evaluated. Throughout the transition period, a significant increase in apelin levels was observed. Various models were employed to identify associations between apelin and the studied metabolic parameters. Notably, significant correlations between apelin and Leptin, Insulin, Cortisol, T3, T4, NEFA, Cholesterol, LDL, VLDL, Total Protein, Albumin, Globulin, Total Bilirubin, Direct Bilirubin and Indirect Bilirubin were observed, with some being immediate while others developed over time. These findings indicate a mutual influence between apelin and specific metabolic indices. Changes in any component of the metabolic profile at one stage can lead to alterations in apelin levels in subsequent stages. The correlations uncovered between apelin and other components of the metabolic profile in transitioning dairy cows offer valuable insights, contributing to a better understanding of the potential effects of apelin on the studied indicators and vice versa., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Chronic kidney disease (CKD) causes specific hormonal disturbances, such as variations in leptin and testosterone levels and function. These disturbances can promote errors in signaling interaction and cellular information processing and can be implicated in the pathogenesis of atherosclerosis. This study investigates the factors that affect leptin in CKD patients and examines how leptin is related to markers of vascular disease. We conducted a cross-sectional study of 162 patients with CKD in pre-dialysis and dialysis stages. We recorded clinical and laboratory data, including leptin, testosterone, and subclinical atherosclerosis markers like brachial-ankle pulse wave velocity (ba PWV) in pre-dialysis CKD patients and flow-mediated vasodilation (FMD) and nitroglycerin-mediated vasodilation (NMD) in hemodialysis (HD) patients. Leptin was significantly correlated with testosterone in CKD pre-dialysis stages ( p < 0.001) and also in HD ( p = 0.026), with adipose tissue mass in pre-dialysis stages ( p < 0.001), and also in HD ( p < 0.001). In women HD patients, leptin correlated with NMD ( p = 0.039; r = -0.379); in all HD patients, leptin correlated with C reactive protein ( p = 0.007; r = 0.28) and parathormone ( p = 0.039; r = -0.220). Our research emphasizes the connection between leptin, adipose tissue, and testosterone in all stages of CKD. Leptin was associated with NMD in HD women and correlated with inflammatory syndrome and parathyroid hormone in all HD patients.

Burns generate every year an important burden of morbidity, being a major global public health problem through prolonged hospitalization, complications, and increased mortality. This study's purpose was to evaluate the serum levels of three adipokines and to establish significant correlations with other circulating molecules and with some clinical parameters. We evaluated 32 children with severe burns (over 25% total burned surface area-TBSA) at 48 h, day 10, and day 21 post burn, and 21 controls. The serum levels of adiponectin, resistin, leptin, tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor-1 (PAI-1), and C-reactive protein (CRP) (among nine other biochemical parameters) were detected by Multiplex technique. Significant statistical differences were obtained for resistin and leptin compared to the control group, in different moments of measurements. Adiponectin serum levels presented statistically significant correlations with hot liquid mechanism of burn, the Revised Baux score, TBSA, resistin, PAI-1, CRP, TNF-α, and triglycerides (TGLs) serum levels. Resistin serum levels presented statistically significant correlations with adiponectin, CRP, PAI-1, leptin, and TNF-α. Additionally, we found statistically significant correlations between leptin serum levels and length of hospitalization, TNF-α, resistin, adiponectin, and PAI-1 serum levels. In severely burned children, adiponectin, resistin, and leptin specifically correlate with clinical parameters and with proteins involved in the systemic inflammatory response and the hypermetabolic response.

Study Objectives: Sleep deprivation is a potential risk factor for metabolic diseases, including obesity and type 2 diabetes. We evaluated the impacts of moderate chronic sleep deprivation on glucose and lipid homeostasis in adult rats., Methods: Wistar rats (both sexes) were sleep-perturbed daily for 2 hours at the early (06:00-08:00) and the late light cycle (16:00-18:00) five days a week (except weekends) for 4 weeks., Results: Sleep perturbation (SP) resulted in reduced body weight gain in both sexes, associated with altered food intake and reduced adiposity. SP did not alter the short- or long-term memories or cause anxiogenic behavior. No major changes were observed in the plasma insulin, leptin, triacylglycerol, non-esterified fatty acids, and blood glucose upon SP. After SP, females exhibited a transitory glucose intolerance, while males became glucose intolerant at the end of the experimental period. Male rats also developed higher insulin sensitivity at the end of the SP protocol. Morphometric analyses revealed no changes in hepatic glycogen deposition, pancreatic islet mass, islet-cell distribution, or adrenal cortex thickness in SP rats from both sexes, except for lower adipocyte size compared with controls. We did not find homogeneous changes in the relative expression of circadian and metabolic genes in muscle or hepatic tissues from the SP rats., Conclusions: Moderate chronic SP reduces visceral adiposity and causes glucose intolerance with a more pronounced impact on male rats, reinforcing the metabolic risks of exposure to sleep disturbances., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background and Objectives: In this study, the effects of a six-week training program and various diets on subfatin, asprosin, irisin, leptin, ghrelin and the lipid profile were investigated in overweight women. Materials and Methods: A total of 78 women voluntarily participated in the study. Groups: The study was divided into eight groups: Healthy Control, Obese Control, Obese + Vegetarian, Obese + Ketogenic, Obese + Intermittent Fasting, Obese + Exercise + Vegetarian, Obese + Exercise + Ketogenic and Obese + Exercise + Intermittent Fasting. While there was no intervention in the healthy and obese control groups, the other groups followed predetermined exercise and diet programs for 6 weeks. Blood samples were taken from the participants in the research group twice (before and after the interventions). An autoanalyzer was used to determine the lipid profile in the blood samples taken, and the ELISA method was used to analyze other parameters. Results: Overall, a significant difference was found in the values of weight, BMI, subfatin, ghrelin, leptin, cholesterol, triglyceride, HDL and LDL as a result of the exercise and diet interventions ( p < 0.05). There was no significant difference in asprosin and irisin values ( p > 0.05). Conclusions: In conclusion, regular exercise and dietary interventions in obese women can regulate lipid profile, ghrelin, leptin and asprosin levels, and increasing irisin with exercise can activate lipid metabolism and support positive changes in lean mass.

Mammals have evolved sex-specific adaptations to reduce energy usage in times of food scarcity. These adaptations are well described for peripheral tissue, though much less is known about how the energy-expensive brain adapts to food restriction, and how such adaptations differ across the sexes. Here, we examined how food restriction impacts energy usage and function in the primary visual cortex (V1) of adult male and female mice. Molecular analysis and RNA sequencing in V1 revealed that in males, but not in females, food restriction significantly modulated canonical, energy-regulating pathways, including pathways associated waith AMP-activated protein kinase, peroxisome proliferator-activated receptor alpha, mammalian target of rapamycin, and oxidative phosphorylation. Moreover, we found that in contrast to males, food restriction in females did not significantly affect V1 ATP usage or visual coding precision (assessed by orientation selectivity). Decreased serum leptin is known to be necessary for triggering energy-saving changes in V1 during food restriction. Consistent with this, we found significantly decreased serum leptin in food-restricted males but no significant change in food-restricted females. Collectively, our findings demonstrate that cortical function and energy usage in female mice are more resilient to food restriction than in males. The neocortex, therefore, contributes to sex-specific, energy-saving adaptations in response to food restriction., Competing Interests: ZP, DK, PM, MR, EO, NR No competing interests declared, (© 2023, Padamsey et al.)

Pre-pregnancy body mass index (pBMI) is a predictor of gestational weight gain (GWG). However, other factors, such as adipokines and inflammation markers, may also be associated with GWG. The aim of the study was to determine the association of leptin, adiponectin, irisin, and C-reactive protein, with GWG in adolescents. A longitudinal study was conducted from 2018 to 2023 in adolescents with a clinically healthy pregnancy. The assessments included sociodemographic and clinical data, pBMI, percent of body fat, serum concentrations of leptin, adiponectin, irisin, and high-sensitivity C-reactive protein (hsCRP), and total GWG adequacy. Cox regression models were performed, the outcome variables were inadequate and excessive GWG. In 198 participants, being overweight/obesity was marginally associated with a protective effect against inadequate GWG (HR = 0.44, 95%CI = 0.18-1.06), regardless of maternal characteristics and adipokines. Leptin (HR = 1.014, 95%CI = 1.008-1.021), and body fat percent (HR = 1.11, 95%CI = 1.05-1.17) were associated with a higher risk of excessive GWG, independent of other maternal variables such as pBMI, while adiponectin was associated with a lower risk. These findings suggest that, in Mexican adolescents, adipose tissue and its adipokines during pregnancy may play a more significant role in the final GWG than body weight.

Background: Craniopharyngioma (CP) is a rare malformational tumor characterized by high rates of recurrence and morbid obesity. However, the role of inflammatory mediators in obesity and the prognosis of patients with CP remains unknown. Therefore, the present study aimed to analyze associations of inflammatory mediators with weight-related outcomes and the prognosis of patients with CP., Methods: A total of 130 consecutive patients with CP were included in this study. The expression levels of seven inflammatory mediators and the plasma leptin concentration were investigated. Clinical parameters, weight changes, new-onset obesity, and progression-free survival (PFS) were recorded. The relationships between inflammatory mediators, clinicopathologic parameters, weight-related outcomes, and PFS were explored., Results: Compared with those in normal pituitary tissue, the expressions of inflammatory mediators in tumor tissue were higher. Higher expression levels of CXCL1 and CXCL8 were identified as independent risk factors for significant weight gain, and CXCL1 and TNF were identified as independent risk factors for new-onset postoperative obesity. Poor PFS was associated with higher expression levels of CXCL1, CXCL8, IL1A, IL6, and TNF., Conclusion: The present study revealed that inflammatory mediators are associated with morbid obesity in patients with CP. Inflammatory mediators may be the critical bridge between elevated leptin and weight-related outcomes. Additionally, PFS was associated with the expression of inflammatory mediators. Further research is needed to elucidate the underlying mechanisms of inflammatory mediators and their potential as targets for novel therapies for CP., (© 2024. The Author(s).)

Importance: Epidemiologic data suggest an association of obesity with breast cancer (BC); however, obesity's contribution to early onset and risk of diagnosis with specific molecular subtypes by race is uncertain., Objective: To examine the race-specific association of body mass index with early onset and diagnosis of specific molecular subtypes., Design, Setting, and Participants: This retrospective cohort study included patients with BC diagnosed between October 1, 2017, and March 31, 2022, at 3 University of South Alabama Mitchell Cancer Institute clinics. Participants were also prospectively enrolled for serum leptin measurement., Main Outcomes and Measures: The primary outcome was age at BC onset and specific subtype diagnosis. The secondary outcome was race-specific differences. Odds ratios (ORs) for associations of body mass index with age at onset and subtype were estimated using the Fisher exact test. Race was self-reported., Results: Of the 1085 study patients, 332 (30.6%) were Black with a median age of 58 (IQR, 50-66) years, and 753 (69.4%) were White with a median age of 63 (IQR, 53-71) years. A total of 499 patients (46.0%) had obesity, with Black women with obesity receiving more frequent BC diagnosis than their White counterparts (OR, 2.40; 95% CI, 1.87-3.15; P < .001). In addition, Black women had a significantly higher incidence of early-onset disease (OR, 1.95; 95% CI, 1.33-2.86; P = .001) than White women, and obesity increased this risk significantly in Black women (OR, 2.92; 95% CI, 1.35-6.22; P = .006). Black women with obesity also had a significantly higher risk of luminal A BC (OR, 2.53; 95% CI, 1.81-3.56; P < .001) and triple-negative BC (TNBC) (OR, 2.48; 95% CI, 1.43-4.22; P = .002) diagnosis than White counterparts. Black women, with or without BC, had significantly higher serum leptin levels (median [IQR], 55.3 [40.3-66.2] ng/mL and 29.1 [21.1-46.5] ng/mL, respectively, P < .001) than White women (median [IQR], 33.4 [18.9-47.7] ng/mL and 16.5 [10.0-22.9] ng/mL, respectively), which was associated with higher odds of luminal A disease (OR, 5.25; 95% CI, 1.69-14.32, P = .003). Higher odds of early-onset disease (OR, 3.50; 95% CI, 0.43-23.15; P = .33 for trend), and TNBC diagnosis (OR, 6.00; 95% CI, 0.83-37.27; P = .14 for trend) were also seen, although these outcomes were not statistically significant., Conclusions and Relevance: In this cohort study of patients with BC, obesity and high serum leptin levels were associated with an enhanced risk of early-onset BC and diagnosis of luminal A and TNBC subtypes in Black women. These findings should help in developing strategies to narrow the existing disparity gaps.

Objective: Preeclampsia (PE) affects only about 10% of women who meet the criteria for obesity based on their body mass index (BMI). Obesity is suggested to play a role in preeclampsia pathophysiology, and in addition to BMI, associated biomarkers with higher sensitivity and specificity, such as with adipokines from adipose tissue, are needed to enable clinical risk assessment. This study aimed to investigate obese pregnant women with and without PE by comparing clinical profiles and adipokine profiles specific to general adipose tissue (adiponectin and leptin)., Materials and Methods: This meta-analysis was conducted following the PRISMA and was registered in PROSPERO (CRD42023478706). We utilized Cochrane, Scopus, and PubMed/Medline databases. The Cochrane ROBINS-I instrument was employed to assess the quality of studies. Pooled standard mean difference (SMD) and p-value were analyzed using a random-effects model with the DerSimonian-Laird method, while subgroup analysis with the Chi-square test and the inconsistency index (I2) were used to assess potential sources of heterogeneity., Results: Three observational studies included a total of 2,646 obese pregnant women and found that adiponectin was more likely to have a lower level in pregnant women with obesity [SMD=-0.32; 95% CI: -0.34-0.17, p=0.003] and leptin was more likely to be higher in obese pregnant women with PE rather than non-PE [SMD=0.53; 95% CI: -0.19-1.08, p<0.00001]., Conclusions: Adiponectin levels were more likely to be lower in pregnant women with obesity in the PE group than in the non-PE group, and leptin levels were more likely to be higher.

Background: Sleep can be affected in patients with chronic spontaneous urticaria (CSU). The mechanisms of sleep regulation remain poorly understood. Orexin-A, a neuroexcitatory peptide, plays a role in coordinating sleep-wake states. Ghrelin and leptin are involved in sleep regulation through the orexin system. Objective: The effects of orexin-A, ghrelin, and leptin on sleep quality in patients with CSU have not been investigated. We aimed to determine the effects of CSU on sleep quality and the association between serum orexin-A, ghrelin, and leptin levels, and sleep quality in patients with CSU. Methods: Thirty-three patients with CSU and 34 sex- and age-matched controls were included in the study. Serum orexin-A, leptin, and ghrelin levels, and the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) scores were measured in patients with CSU and in the controls; also used were the chronic urticaria quality-of-life questionnaire score and the urticaria activity score used for 7 consecutive days. Results: Median (minimum-maximum) orexin-A, leptin, and ghrelin levels in patients were 385 pg/mL (90-495 pg/mL), 3.1 ng/mL (0-21.2 ng/mL), and 701.8 pg/mL (101.9-827.7 pg/mL), respectively. Median serum orexin-A and leptin levels were higher in the patients compared with the controls (p < 0.001 and p = 0.012, respectively), whereas the median serum ghrelin levels were similar to the controls (p = 0.616). The serum orexin-A level was positively correlated with ghrelin (r = 0.298, p = 0.014), PSQI sleep quality (r = 0.356, p = 0.003), and ESS (r = 0.357, p = 0.003). Conclusion: Serum orexin-A is associated with sleep quality in patients with CSU. Further studies are needed to elucidate the role of ghrelin and leptin on sleep quality in patients with CSU.