American journal of physiology. Endocrinology and metabolism最新文献

{"title":"Validation in adult Black and White women of the ISS model for estimating insulin sensitivity and beta-cell function from mixed-meal tests.","authors":"Arthur S Sherman, Nathan Sala, Anne E Sumner, Joon Ha, Stephanie T Chung","doi":"10.1152/ajpendo.00397.2025","DOIUrl":"10.1152/ajpendo.00397.2025","url":null,"abstract":"<p><p>The Insulin Sensitivity and Secretion (ISS) differential equation model has been previously shown to provide simultaneous estimates of insulin sensitivity (SI) and beta-cell function (BCF) during an oral glucose tolerance test. Using the Federal Women's Study, we adapted the ISS model to fit glucose and insulin dynamics and estimate SI and BCF during mixed-meal tests (MMTs). Our goal was to develop an effective, straightforward, and reliable tool that would be simpler to use than currently available approaches that require technically challenging deconvolution methods to assess BCF. The ISS model for mixed-meal tests strongly correlated with oral glucose tolerance tests and gold-standard estimates from intravenous glucose tolerance tests and was reliable when using a shortened 2-h MMT protocol. The ISS model is versatile, publicly available, and expands the toolbox for assessing postprandial glucose-insulin homeostasis.<b>NEW & NOTEWORTHY</b> We have previously validated a differential equation model (the ISS model) to determine insulin sensitivity and beta-cell function from oral glucose tolerance tests. The ISS model is simpler to use and requires less data than other current models. We have now extended this model of glucose-insulin metabolism for use with mixed-meal tolerance tests; MMTs may be preferred because they are more physiological and closer to what people eat in daily life.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E459-E467"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic drivers of thermogenic adipose tissue dysfunction in aging and obesity.","authors":"Gabriela Ueta Ortiz, Gabriela Ferreira Abud, Caroline Fogagnolo, Sofia Germano Travieso, Adelino Sanchez Ramos da Silva, Ellen Cristini de Freitas","doi":"10.1152/ajpendo.00105.2026","DOIUrl":"10.1152/ajpendo.00105.2026","url":null,"abstract":"<p><p>Population aging is accelerating worldwide and is accompanied by a growing burden of chronic metabolic diseases. Adipose tissue dysfunction represents a central mechanism linking aging and obesity to metabolic decline, contributing to chronic low-grade inflammation, impaired adipokine signaling, ectopic lipid deposition, and the whitening of thermogenic fat depots. Brown adipose tissue (BAT) plays a key role in adaptive thermogenesis through uncoupling protein 1 (UCP-1)-mediated mitochondrial uncoupling; however, its activity progressively declines with advancing age and excess adiposity. This narrative review synthesizes emerging biomolecular mechanisms that underlie impaired thermogenic function in the context of aging and obesity. We integrate evidence across three major regulatory domains: <i>1</i>) intracellular thermogenic signaling, highlighting salt-inducible kinases (SIK2/3), as transcriptional repressors that limit UCP-1 expression when β3-adrenergic/protein kinase A (PKA) signaling is impaired; <i>2</i>) autophagy-dependent secretion of acyl-CoA-binding protein (ACBP), which suppresses lipolysis, β-oxidation, and thermogenic signaling and may contribute to BAT whitening; and <i>3</i>) immune-mediated regulation of thermogenic adipose tissue, with macrophage-modulating sympathetic signaling, inflammatory tone, and extracellular matrix remodeling through pathways involving NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome -monoamine oxidase A (MAOA), slit guidance ligand 3 (SLIT3)/ETS1, prolidase (PEPD), and immunoglobulin G (IgG). Collectively, these convergent mechanisms illustrate how aging and obesity impose coordinated constraints on brown and beige adipose tissue activation. By framing thermogenic decline as a regulated process, this review provides a conceptual basis for future studies aimed at preserving metabolic flexibility and promoting healthier aging.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E439-E449"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucose-lowering in type 2 diabetes may be mediated by improved proinsulin processing without better β-cell compensation.","authors":"Ravi Retnakaran, Junwei Shen, Mihir Parikh, Anthony J Hanley, Bernard Zinman, Jacqueline L Beaudry","doi":"10.1152/ajpendo.00163.2026","DOIUrl":"10.1152/ajpendo.00163.2026","url":null,"abstract":"<p><p>In type 2 diabetes (T2DM), glucose-lowering is typically achieved by enhancing the capacity of the pancreatic beta-cells to compensate for ambient insulin resistance. Impaired processing of proinsulin, as reflected by an elevated ratio of fasting serum proinsulin to C-peptide (PI:C), is a marker of beta-cell stress but not compensation. Indeed, it is unclear whether enhancing proinsulin processing alone can improve glycemic control in T2DM. We thus sought to evaluate the impact of proinsulin processing on glucose-lowering in a recently reported clinical trial in which 90 adults with T2DM (mean A1c 6.5% ± 0.7%) were randomized to 8-wk treatment with <i>1</i>) basal insulin glargine (Glar), <i>2</i>) glargine plus thrice-daily meal insulin lispro (Glar/Lispro), or <i>3</i>) glargine plus twice-daily administration of the glucagon-like peptide-1 receptor agonist exenatide (Glar/Exe). At baseline, after 8-wk treatment and again after subsequent 12-wk washout, participants underwent assessment of insulin sensitivity/resistance [Matsuda index; Homeostasis Model of Assessment of Insulin Resistance (HOMA-IR)], beta-cell compensation (Insulin Secretion-Sensitivity Index-2; insulinogenic index/HOMA-IR; ΔCpeptide_0-120/Δglucose_0-120 × Matsuda; ΔISR_0-120/Δgluc_0-120 × Matsuda), and proinsulin processing (fasting PI:C). At 8-wk, both A1c (6.2% ± 0.4% vs. 5.9% ± 0.5% vs. 5.8% ± 0.4%, <i>P</i> = 0.007) and fasting PI:C (0.013 ± 0.011 vs. 0.009 ± 0.006 vs. 0.008 ± 0.005, <i>P</i> = 0.01) progressively decreased from Glar to Glar/Lispro to Glar/Exe, with no differences between the groups in Matsuda index, HOMA-IR, or any of the four measures of beta-cell compensation. In mediation analyses, fasting PI:C emerged as the sole biologic mediator of the respective A1c treatment effects of Glar/Lispro (<i>P</i> = 0.03) and Glar/Exe (<i>P</i> = 0.01) vs. Glar. In conclusion, it thus emerges that glucose-lowering in T2DM may be achieved through improved proinsulin processing without better beta-cell compensation.<b>NEW & NOTEWORTHY</b> In this report, mediation analyses identify the fasting proinsulin-to-C-peptide ratio as a biologic determinant of the A1c treatment effect observed in a recently reported clinical trial in which the study interventions had no differential effect on pancreatic beta-cell compensation. These findings suggest that glucose-lowering may be achieved through improved proinsulin processing without better beta-cell compensation, supporting consideration of proinsulin biology as a potential novel therapeutic target in the management of type 2 diabetes.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E491-E499"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced behavioral responses to ghrelin administration are unaffected by ghrelin deficiency in a DHT-induced PCOS mouse model.","authors":"Karina Prins, Li Meng, Anke McLuskey, Martin Huisman, Jacobie Steenbergen, Patric J D Delhanty, Jenny A Visser","doi":"10.1152/ajpendo.00108.2026","DOIUrl":"10.1152/ajpendo.00108.2026","url":null,"abstract":"<p><p>Polycystic ovary syndrome [recently renamed to polyendocrine metabolic ovarian syndrome (PMOS)] is the most common endocrine disorder in women of reproductive age. Women with PMOS not only suffer from reproductive symptoms but are also more prone to develop metabolic dysfunction and aberrant eating behavior. The gut hormone ghrelin affects both metabolism and eating behavior in a sex-dependent fashion. Therefore, this study explored the effects of ghrelin deficiency on the phenotype of female mice with prepubertal, chronic dihydrotestosterone (DHT) exposure, a widely used mouse model of PMOS. DHT exposure markedly suppressed estrus cycling and corpora lutea number, increased lean mass (but not fat mass), and elevated inactive-phase food intake, but ghrelin deficiency had no marked effect on these outcomes. Interestingly, in wild-type mice, eating time and meal number of DHT-treated mice responded more strongly to acute ghrelin administration than those of controls. In ghrelin-deficient mice, responses to acute ghrelin administration were like DHT-treated wild-type mice, regardless of treatment. Besides effects on eating behavior, chronic DHT exposure also reduced locomotor activity in both wild-type and ghrelin-deficient mice, which is in line with reports on physical activity in women with PMOS. Locomotor activity was also decreased upon acute ghrelin administration, especially in ghrelin-deficient mice. Overall, chronic DHT exposure modified the behavioral responses to acute ghrelin administration in females, without evidence for additive effects of ghrelin deficiency, suggesting overlapping mechanisms of action. This work emphasizes the added value of detailed behavioral data in translational models of human disease to help elucidate potential mechanisms underlying aberrant eating behavior.<b>NEW & NOTEWORTHY</b> This study uniquely examined how ghrelin deficiency interacts with prepubertal chronic DHT exposure, a PMOS mouse model, shaping metabolism and eating behavior in female mice. Although ghrelin deficiency minimally altered DHT-induced reproductive or metabolic phenotypes, chronic DHT exposure affected behavioral responses to acute ghrelin, indicating interacting mechanisms between androgen and ghrelin signaling in PMOS. This work highlights the importance of detailed behavioral assessment of translational models of disease to explore mechanisms behind aberrant behavior.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E479-E490"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Additive effects of metformin on glucose homeostasis after metabolic-bariatric surgery in nonobese insulin-deficient diabetic rats.","authors":"Mélanie Hirlemann, Mélanie Garmon, Lara Ribeiro-Parenti, Danielle Bailbé, Alexandra Willemetz, Hounayda El-Jindi Shahrour, Jamileh Movassat, Claire Carette, Maude Le Gall","doi":"10.1152/ajpendo.00077.2026","DOIUrl":"10.1152/ajpendo.00077.2026","url":null,"abstract":"<p><p>This study investigates the individual and combined effects of Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and metformin on glucose regulation in a nonobese, insulin-deficient model of type 2 diabetes. Female Goto-Kakizaki (GK) rats underwent RYGB, SG, or sham surgery. Three weeks postoperatively, animals received metformin (50 mg/kg/day, 5 days/wk) or vehicle for three additional weeks. Glucose tolerance was assessed using a standardized meal test, and insulin sensitivity was evaluated by an insulin tolerance test. Plasma levels of glucagon like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin, and leptin were measured. RYGB and SG reduced body weight, food intake, and leptin levels, and improved fasting glucose, glucose tolerance, insulin sensitivity, and postprandial incretin and insulin secretion. Metformin alone improved glucose tolerance and insulin sensitivity independently of incretin or insulin changes. When combined with surgery, metformin further reduced postprandial glycemic excursions but did not enhance insulin sensitivity or hormone secretion beyond surgery alone. In conclusion, metabolic-bariatric surgery and metformin independently improve glucose regulation in nonobese diabetic GK rats. Their combination provides additional benefits on postprandial glucose control, despite no additional effects on insulin sensitivity or hormone levels. These findings support the use of metformin as an adjunct to metabolic-bariatric surgery in insulin-deficient diabetes and highlight the need for longer-term, sex-inclusive studies to enhance translational relevance.<b>NEW & NOTEWORTHY</b> Metabolic-bariatric surgery and metformin each improved glucose regulation in nonobese, insulin-deficient female GK rats. Their combination further reduced postprandial glycemic excursions without additional effects on insulin sensitivity or incretin/insulin secretion. These findings demonstrate that metformin retains metabolic activity after metabolic-bariatric surgery and improves postprandial glucose control through mechanisms distinct from surgery-induced incretin pathways. This study contributes to the ongoing discussion regarding metformin use after metabolic-bariatric surgery, particularly in insulin-deficient diabetes.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E501-E510"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipocyte β3-adrenergic receptor signaling attenuates leptin production but is dispensable for fasting induced leptin suppression.","authors":"Samuel R Heaselgrave, Steven C Wyler, Shreya Thomas, Arely Tinajero, Marco Galvan, Emma Mihaila, Roger Fan, Teppei Fujikawa, Philipp E Scherer, Joel K Elmquist","doi":"10.1152/ajpendo.00083.2026","DOIUrl":"10.1152/ajpendo.00083.2026","url":null,"abstract":"<p><p>Leptin, secreted by adipocytes, conveys the status of peripheral energy stores to the brain to regulate appetite and metabolism. Although sympathetic activation via β3-adrenergic receptors (β3-ARs) has been shown to suppress leptin expression, it remains unclear whether this regulation arises directly within adipocytes or through other populations. In addition, it is unclear whether β3-AR signaling contributes to the fasting-induced reduction in leptin. To address this, we generated a novel <i>Adrb3</i> transcriptional block mouse (<i>Adrb3</i>^TB/TB) enabling global β3-AR inactivation and adipocyte-specific reexpression (<i>Adrb3</i>^TB/TB; <i>Adipoq</i>-Cre). Global loss of <i>Adrb3</i> increased plasma leptin levels, whereas reexpression in adipocytes normalized leptin and restored β3-AR agonist-induced leptin suppression. Analysis of <i>Lep</i> mRNA revealed depot-specific regulation, with β3-AR signaling predominantly affecting gonadal and subcutaneous white adipose tissue, whereas brown adipose tissue responses were modest and variable. Despite these effects, fasting for 48 h comparably reduced plasma leptin and <i>Lep</i> mRNA in both wild-type (WT) and <i>Adrb3</i>^TB/TB mice, indicating that β3-AR signaling is not required for the fasting-induced decline in leptin. Collectively, these findings establish adipocyte β3-AR signaling as a key regulator that constrains leptin synthesis under basal and stimulated conditions in male mice, but not during energy deprivation. Together, these findings clarify the role of adipocyte β3-adrenergic signaling in leptin regulation and provide new insight into the sympathetic control of adipose tissue function.<b>NEW & NOTEWORTHY</b> This study introduces a novel Adrb3 transcriptional block mouse model that enables global inactivation or adipocyte-specific reexpression of β3-adrenergic receptor signaling. Using this approach, we demonstrate that adipocyte β3-adrenergic signaling directly restrains leptin production under basal and stimulated conditions but is dispensable for fasting-induced leptin suppression. These findings refine the role of sympathetic signaling in adipose tissue and clarify mechanisms governing leptin regulation.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E450-E458"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13622890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A noninvasive ¹³C-mannitol breath test to monitor semaglutide treatment-induced delayed oral-cecal transit in mice.","authors":"Daniel E Vieira, Emily M Langmeyer, Marissa D Cortopassi, William B Rubio, Sarah N Flier, Lynn Bry, Alexander S Banks","doi":"10.1152/ajpendo.00113.2026","DOIUrl":"10.1152/ajpendo.00113.2026","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as semaglutide, are highly effective treatments for obesity and type 2 diabetes but are often associated with gastrointestinal side effects including delayed transit times through the gastrointestinal tract. We present a noninvasive breath test to measure oral-cecal transit time (OCTT) in mice that could be readily translated to clinical studies. Current methods for measuring OCTT are limited by invasiveness, terminal procedures, anesthesia, radioactive tracers, or stress-induced influence on the outcomes. Here we demonstrate that ¹³C-labeled mannitol is metabolized by murine cecal microbiota, producing measurable ¹³CO₂ in exhaled breath. Using indirect calorimetry combined with real-time measurement of the ¹³C/¹²C ratio, this approach provides a highly granular, noninvasive method to measure OCTT in mice. This technique is performed in unrestrained freely moving animals while enabling high-throughput measurements performed longitudinally. The method improves experimental rigor and reproducibility and provides a valuable tool for studying gastrointestinal physiology and the effects of pharmacologic therapies.<b>NEW & NOTEWORTHY</b> A novel noninvasive assay uses orally administered ¹³C-mannitol, metabolized by cecal microbiota into exhaled ¹³CO₂, to enable continuous, longitudinal measurement of oral-cecal transit time in unanesthetized, freely moving mice via indirect calorimetry with isotope ratio analysis. Pharmacological validation confirmed sensitivity to delayed transit, including a pronounced semaglutide-induced delay in obese mice that models a clinically relevant glucagon-like peptide-1 (GLP-1) receptor agonist adverse effect.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E468-E478"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Females with normal-weight obesity display evidence of postprandial dyslipidemia and basal intestinal permeability.","authors":"Alexis R Quirk, Jenna K Schifferer, Brooklyn R Cline, Emily R Wolf, Dhanya O Pathangi, Quinn E Bowling, Amna Mallick, Lydia R Wiersma, Natalie G Keirns, Bryant H Keirns","doi":"10.1152/ajpendo.00192.2026","DOIUrl":"10.1152/ajpendo.00192.2026","url":null,"abstract":"<p><p>Females with a normal body mass index (BMI) and high body fat percent (i.e., normal-weight obesity or NWO) are at increased risk for cardiometabolic diseases compared with normal-weight lean (NWL) counterparts. However, underlying mechanisms remain unclear. Here, we examined postprandial lipids, gut permeability biomarkers, and arterial stiffness outcomes as potential factors implicated in cardiometabolic disease development. Females (<i>N</i> = 33) with a normal BMI were grouped as NWO (body fat percent ≥33.0%; <i>n</i> = 18) or NWL (body fat percent <33.0; <i>n</i> = 15). Following intravenous insertion and baseline blood collection, a high-fat meal was consumed. Additional blood samples were collected at 1-, 2-, 3-, and 4-h postmeal for determination of lipids [triglycerides, high-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo) B] and intestinal permeability biomarkers [lipopolysaccharide binding protein (LBP), soluble cluster differentiation 14 (sCD14), LBP:sCD14]. Pulse wave analysis and pulse wave velocity were measured as indicators of arterial stiffness at 0, 2, and 4 h. Across both groups, the high-fat meal impacted triglycerides (increased), HDL-C (decreased), and apolipoprotein-B (decreased; <i>P</i>_Time ≤ 0.001). The frequency of adverse postprandial triglyceride responses was higher in NWO compared with NWL females (<i>P</i> < 0.05). Furthermore, nonsignificant (<i>P</i>_Group ≤ 0.08), medium effect sizes ([Formula: see text] ≥ 0.12) were observed for triglycerides and apoB, consistent with NWO > NWL, regardless of time point. LBP and LBP:sCD14 increased, whereas sCD14 decreased, following the high-fat meal (<i>P</i>_Time ≤ 0.05). In addition, NWO had higher LBP regardless of time point compared with NWL (<i>P</i>_Group < 0.05). All arterial stiffness measures decreased postmeal (<i>P</i>_Time ≤ 0.05). In conclusion, this work provides early evidence of postprandial dyslipidemia and basal intestinal hyperpermeability in females with NWO.<b>NEW & NOTEWORTHY</b> We present new evidence that females with normal-weight obesity are characterized by postprandial dyslipidemia and basal intestinal permeability, which may be implicated in their documented cardiometabolic disease risk.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E512-E519"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise-mimicking effect of exogenous lactate administration: Promoting visceral fat reduction via ventromedial hypothalamic SF-1 neurons in female rats.","authors":"Jinchan Du, Zhaomin Zhang, Jing Han, Shuai Tian, Mengmeng Chang, Wei Chen, Yang Liu","doi":"10.1152/ajpendo.00059.2026","DOIUrl":"https://doi.org/10.1152/ajpendo.00059.2026","url":null,"abstract":"<p><p>Lactate, a metabolic product of high-intensity training, may possess exercise-mimicking effects that promote fat loss via the hypothalamic-adipose axis, yet its neuronal targets remain unclear. This study investigated whether lactate administration mimics HIT-induced fat loss through steroidogenic factor-1 (SF-1) neurons in the ventromedial hypothalamus (VMH). Female SD rats fed a high-fat diet were subjected to a 6-week intervention. The results showed that chronic lactate administration independently reduced Visceral adipose tissue (VAT) mass and enhanced the resting fat oxidation rate more effectively than moderate-intensity aerobic training (AT), which conversely suppressed post-exercise lipolysis. The VAT loss was accompanied by neuroplastic changes in the VMH and upregulated markers of sympathetic capacity in adipose tissue. In contrast, chemogenetic inhibition of VMH SF-1 neurons using DREADDs reversed the lactate-mediated electrophysiological changes and abolished the elevation in resting metabolic rate (RMR), confirming the necessity of this neuronal population for the metabolic effects of lactate. These findings demonstrate that lactate acts as a central exerkine, activating VMH SF-1 neurons, which correlates with an upregulated capacity for SNS-mediated VAT reduction, thereby providing a mechanistic explanation for the superior efficacy of HIT in managing central obesity.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the role of Brain-Derived Neurotrophic Factor as a biomarker in female infertility: A systematic review and meta-analysis.","authors":"Ariane M Zanesco, Natália S Tonet, Maisa M Araújo, Patrícia B Botelho, Licio A Velloso","doi":"10.1152/ajpendo.00125.2026","DOIUrl":"https://doi.org/10.1152/ajpendo.00125.2026","url":null,"abstract":"<p><p>Brain-derived neurotrophic factor (BDNF) is essential for neuronal survival and development, and is also involved in oogenesis, follicle recruitment, and germ cell survival, which could impact reproduction. However, in humans, the relationship between BDNF levels and infertility remains controversial. The aim of this systematic review and meta-analysis was to explore the available evidence on the variation of BDNF levels in the body fluids of women and men and their interface with different conditions that could affect reproductive functions. Data were independently extracted by 2 reviewers. A systematic search was performed on six databases. Of the 1,735 studies identified, 20 were included in the qualitative synthesis and 15 in the meta-analysis. Meta-analysis was performed for all studies regarding infertility markers, and then, specifically, only for studies that evaluated endometriosis and other cases of infertility. Of the 20 studies included in the systematic review, only 1 evaluated sperm dysfunction in men. Of the 19 studies conducted in women, 13 evaluated endometriosis, 4 evaluated amenorrhea, 1 evaluated premature ovarian failure, and 1 evaluated different outcomes on childbirth. In the meta-analysis, BDNF levels were associated with endometriosis and other conditions that lead to infertility. Our findings confirm that BDNF levels are dysregulated in infertility conditions. However, the analyses showed substantial heterogeneity and, in some cases, evidence of publication bias. Further studies evaluating infertility in men and that include BMI, estrogen levels, and the menstrual cycle phase at the time of collection in women are crucial for obtaining more robust results.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}