American journal of physiology. Endocrinology and metabolism最新文献

{"title":"Postbiotic gut bacteria site-specific immunomodulators improve liver steatosis, inflammation, and fibrosis in obese mice with MASLD.","authors":"Rodrigo Rodrigues E-Lacerda, Nicole G Barra, Meghan O Conn, Dana Kukje Zada, Nazli Robin, Han Fang, Daniel M Marko, Neeraja Punde, Shirin Kalyan, Hal Gunn, Jonathan D Schertzer","doi":"10.1152/ajpendo.00488.2025","DOIUrl":"10.1152/ajpendo.00488.2025","url":null,"abstract":"<p><p>Obesity promotes metabolic dysfunction-associated steatotic liver disease (MASLD). Gut microbiota can influence MASLD through local communication between the gut and liver. Bacterial components are often conceptualized only as contributors to chronic inflammation. However, certain postbiotics can protect against chronic inflammation and dysmetabolism by activating specific immune responses during obesity. Site-specific innate immune training can direct compartmentalized immune responses. We hypothesized that site-specific immunomodulation by gut-derived inactivated bacterial-based stimuli (i.e., postbiotics) would improve features of MASLD. We found that biweekly subcutaneous injections of an inactivated bacterial preparation of a gut bacterium (QBECO from <i>Escherichia coli</i>) improved markers of steatosis, inflammation, and fibrosis indicative of MASLD in obese mice. QBECO lowered liver mass, triglycerides, F4/80 macrophages, eosinophil peroxidase activity, and collagen content in the liver without altering food intake or body mass in obese mice. QBECO increased whole body lipid oxidation without altering total energy expenditure in obese mice. QBECO had an immunomodulatory effect that lowered liver eosinophil peroxidase activity, lowered liver nitrite/arginase ratio, and increased CD163 positive cells, a marker of M2 macrophages in the liver of obese mice. We confirmed that multiple gut bacteria-derived postbiotics improved MASLD as injections of an inactivated bacterial preparation of <i>Proteus mirabilis</i> (QBPMI) also lowered markers of steatosis, inflammation, and fibrosis in obese mice. A postbiotic from <i>Klebsiella variicola</i> (QBKPN), a bacterium typically pathogenic outside the gut, did not alter MASLD in obese mice. Therefore, site-specific immunomodulators derived from gut bacteria can improve the hallmarks of MASLD without causing weight loss.<b>NEW & NOTEWORTHY</b> This study demonstrates that site-specific immunomodulators (SSIs), prepared from inactivated bacteria, can attenuate liver steatosis, inflammation, and fibrosis in a mouse model of obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Gut bacteria-derived SSIs improved hallmarks of MASLD without altering body weight or food intake, but an SSI derived from a bacterium typically pathogenic outside the gut did not alter MASLD. Therefore, gut-derived SSI postbiotics can improve MASLD.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E267-E275"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997004","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":"Synergistic potential of TREM2 agonists and exercise training in Alzheimer's disease.","authors":"Jinmin Zhang, Barbara St Pierre Schneider, Elias Muguerza, Eunhee Chung, Chia George Hsu","doi":"10.1152/ajpendo.00124.2025","DOIUrl":"10.1152/ajpendo.00124.2025","url":null,"abstract":"<p><p>Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglia-enriched receptor that regulates phagocytosis, lipid metabolism, and inflammation resolution in the brain. Loss or mutation of TREM2, including the R47H variant, impairs amyloid-β clearance and lipid handling, thereby increasing the risk and accelerating the progression of Alzheimer's disease (AD). TREM2 signaling couples debris recognition with mitochondrial activation and fatty acid oxidation, maintaining microglial energy balance and promoting a reparative phenotype. Pharmacologic TREM2 agonists, such as AL002, DNL919, and VG-3927, enhance microglial survival, plaque compaction, and mitochondrial respiration in AD models, although clinical efficacy may depend on disease stage and metabolic fitness. Exercise training represents a complementary strategy that similarly enhances TREM2 expression, restores microglial homeostasis, and improves mitochondrial metabolism. Both aerobic and resistance exercise activate TREM2-dependent signaling pathways to reduce neuroinflammation and support synaptic integrity. Collectively, these findings highlight TREM2 as a central immunometabolic regulator and suggest that combining TREM2-targeted therapeutics with exercise may offer a synergistic strategy to slow neurodegeneration in AD.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E298-E308"},"PeriodicalIF":3.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909728","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":"Substrate utilization during short-term fasting in older men and women.","authors":"San Y Wang, Rita H Tsay, Danya Zhang, Naomi K Fukagawa","doi":"10.1152/ajpendo.00530.2025","DOIUrl":"10.1152/ajpendo.00530.2025","url":null,"abstract":"<p><p>Older people are prone to involuntary fasting, but systematic assessment of their mobilization and oxidation of the three macronutrients during fasting has not been previously reported. Because of changes in body composition and metabolic regulatory pathways with aging, older people might have different kinetics of utilization of macronutrient stores during fasting than younger people. We measured body composition by dual-energy X-ray absorptiometry and studied the effects of a 36-h fast on protein mobilization, lipolysis, glucose output, and protein, fat, and carbohydrate oxidation in 10 older (60-81 yr) and 10 younger (18-35 yr) healthy adults. A 36-h fast induced a pronounced shift toward fat oxidation: in the postabsorptive state, fat oxidation averaged 52%-55% of resting energy expenditure (REE) and increased to 63%-68% after fasting, with corresponding decreases in carbohydrate oxidation. Protein oxidation decreased with fasting but still contributed 16%-18% of REE in older participants. For several metabolic variables (respiratory exchange ratio, glucose <i>R</i>_a, glycerol <i>R</i>_a, urea <i>R</i>_a, urea excretion, and percent of REE from carbohydrate and fat), we observed significant age × fasting interactions (<i>P</i> < 0.01). Younger adults exhibited larger decreases in glucose <i>R</i>_a and greater increases in markers of protein turnover (leucine <i>R</i>_a, urea production) and lipolysis, whereas older adults showed blunted glucose and leucine responses but maintained substantial protein oxidation. These age-related differences suggest that older adults rely relatively more on ongoing protein catabolism during short-term fasting, which may contribute to vulnerability to muscle loss during illness or prolonged inadequate intake.<b>NEW & NOTEWORTHY</b> A 36-h fast had a profound effect on substrate utilization in older women and men. In the postabsorptive state, fat oxidation averaged 52%-55% of REE. After a 36-h fast, fat oxidation increased to 63%-68%, with corresponding decreases in carbohydrate oxidation. The continued reliance on protein oxidation (16%-18% of REE) with fasting may be an important factor in the muscle loss seen in older adults with chronically inadequate food intake and impaired physical activity.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E356-E368"},"PeriodicalIF":3.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117570","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":"Impact of obesity on aromatic amino acids and brain glucose during acute hyperglycemia.","authors":"Brooke C Matson, Felona Gunawan, Douglas L Rothman, Graeme F Mason, Olga Ilkayeva, Christopher B Newgard, Janice J Hwang","doi":"10.1152/ajpendo.00463.2025","DOIUrl":"10.1152/ajpendo.00463.2025","url":null,"abstract":"<p><p>Hyperaminoacidemia is an early hallmark of insulin resistance, with aromatic and branched chain amino acids particularly associated with insulin resistance and type 2 diabetes. We previously showed that healthy adults with obesity exposed to acute hyperglycemia have lower brain glucose levels measured by magnetic resonance spectroscopy than lean controls, suggesting that a blunted brain response to hyperglycemia may be an early marker of insulin resistance. Here, in a secondary analysis of our prior study, we used targeted mass spectrometry-based metabolomics to measure plasma amino acids in participants with and without obesity to determine whether changes in peripheral metabolites associated with early insulin resistance such as amino acids were associated with changes in brain glucose levels during hyperglycemia. There were few differences in baseline amino acids between groups, but acute hyperglycemia unveiled higher plasma concentrations of amino acids including cysteine, cystine, glutamic acid, glutamine, methionine, and aromatic amino acids in obesity. Plasma glucagon levels were also higher in obesity during acute hyperglycemia. Higher plasma concentrations of aromatic amino acids and glucagon were significantly correlated with lower brain glucose levels, illustrating parallel development of central and peripheral metabolic changes in obesity.<b>NEW & NOTEWORTHY</b> We related early insulin resistance-associated peripheral factors with brain glucose measured by ¹³C magnetic resonance spectroscopy during acute hyperglycemia in young, healthy adults with and without obesity. Plasma amino acids including aromatic amino acids and glucagon were higher in obesity during acute hyperglycemia. There were negative correlations between aromatic amino acids and glucagon with the change in brain glucose. These findings may be related to brain oxidative stress and neurotransmitter synthesis in obesity.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E346-E355"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13036701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117546","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":"Colocalization and functional analyses identify <i>GBE1</i> as a gene linking muscle strength and cardiometabolic fitness.","authors":"Theresia M Schnurr, Miranda L Johnson, Christopher Jin, Kimmie V Sørensen, Lindsey Kim, James W Jahng, Amanda Ramste, Ewa Bielczyk-Maczynska, Michael J Gloudemans, Peter Saliba-Gustafsson, Elena Vinton, Patrick L Jurney, Ivan Carcamo-Orive, Euan A Ashley, Torben Hansen, Joshua W Knowles, Brian T Palmisano","doi":"10.1152/ajpendo.00470.2025","DOIUrl":"10.1152/ajpendo.00470.2025","url":null,"abstract":"<p><p>Handgrip strength is a proxy for muscular fitness, an indicator for general health status, and is associated with cardiometabolic health. The mechanisms connecting handgrip strength to skeletal muscle function are incompletely understood. We applied integrated linkage-disequilibrium-adjusted colocalization analysis of genome-wide association study summary statistics for handgrip strength, combined with expression and splicing quantitative trait loci from skeletal muscle, and identified glycogen branching enzyme 1 (<i>GBE1</i>) as a candidate gene for handgrip strength. CRISPR-interference knockdown of <i>GBE1</i> in immortalized human skeletal muscle cells (HMCL-7304) demonstrated decreased glycogen content and accumulation of polyglucosan bodies. Knockdown of <i>GBE1</i> led to increased oxygen consumption rate, oxidative stress, and changes in mitochondrial morphology. Transcriptomic profiling of <i>GBE1</i> knockdown cells identified upregulation of the human superoxide dismutase 2 and enrichment of pathways related to muscle contraction and oxidative stress responses. These functional genomic analyses prioritize <i>GBE1</i> as a muscle-relevant candidate gene for handgrip strength and provide mechanistic insights to muscle fitness.<b>NEW & NOTEWORTHY</b> Colocalization of genome-wide association study (GWAS) loci with quantitative trait loci (QTL) in skeletal muscle tissue identified <i>GBE1</i> as a candidate for handgrip strength. Cellular phenotypes with <i>GBE1</i> knockdown in immortalized human skeletal muscle cells include decreased glycogen content, accumulation of polyglucosan bodies, changes in mitochondrial function and morphology, and increased expression of reactive oxygen species (ROS) scavengers. Transcriptomic changes suggest a role for <i>GBE1</i> in muscle contraction and oxidative stress-mediated responses.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E380-E389"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13008485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146206376","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":"Changes in body composition and resting energy expenditure during the first year after Roux-en-Y or one-anastomosis gastric bypass.","authors":"Jari E Karppinen, Sini Heinonen, Tuure Saarinen, Birgitta W van der Kolk, Ulla Säiläkivi, Henna Sammalkorpi, Anne K Penttilä, Per-Henrik Groop, Anne Juuti, Kirsi H Pietiläinen","doi":"10.1152/ajpendo.00185.2025","DOIUrl":"10.1152/ajpendo.00185.2025","url":null,"abstract":"<p><p>Resting energy expenditure (REE) declines during weight loss because of both organ-tissue mass loss and adaptive thermogenesis, but their relative contributions after bariatric surgery remain unclear. Our primary aim was to quantify these components during the first postoperative year and secondarily to compare Roux-en-Y gastric bypass (RYGB) with one-anastomosis gastric bypass (OAGB). Forty-two adults with obesity (RYGB, <i>n</i> = 21; OAGB, <i>n</i> = 21) underwent dual-energy X-ray absorptiometry (DXA) before surgery and at 6 and 12 mo, and organ-tissue masses were estimated using MRI-derived prediction equations. A smaller subset of 29 participants (RYGB, <i>n</i> = 15; OAGB, <i>n</i> = 14) had valid indirect calorimetry measurements for REE analysis. Participants lost 27.3 kg (21%) of baseline body weight at 6 mo and 32.3 kg (25%) at 12 mo, with no significant differences between procedures in the DXA-measured body composition outcomes or calculated organ-tissue masses. Measured REE decreased by 383 kcal/day at 6 mo (<i>P</i> < 0.001), of which 168 kcal/day [95% confidence interval (CI): 59-276, <i>P</i> = 0.004] was attributed to adaptive thermogenesis. At 12 mo, REE remained 315 kcal/day below baseline (<i>P</i> < 0.001), but adaptive thermogenesis was not statistically detectable (89 kcal/day; 95% CI: -19 to 198, <i>P</i> = 0.11). Adaptive thermogenesis did not significantly differ between procedures. In conclusion, ∼44% of the early 6-mo postoperative decline in REE was associated with adaptive thermogenesis, with the remaining ∼56% associated with organ-tissue mass loss. Adaptive thermogenesis was no longer clearly evident at 12 mo. RYGB and OAGB resulted in similar changes in body composition and REE.<b>NEW & NOTEWORTHY</b> Resting energy expenditure declines after bariatric surgery, but the relative roles of tissue loss and adaptive thermogenesis are unclear. Using DXA-based organ-tissue estimates with indirect calorimetry, we show that adaptive thermogenesis accounted for ∼44% of the 6-mo postoperative REE decline, with the remainder due to tissue loss. Adaptive thermogenesis was not robustly detectable at 12 mo. Roux-en-Y and one-anastomosis gastric bypass show similar body composition and REE changes.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E287-E297"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008538","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":"Impact of <i>AKR1C2</i> and <i>AKR1C3</i> single-nucleotide polymorphism rs28571848 in adipose tissues of individuals with severe obesity.","authors":"Giada Ostinelli, Alan Ramalho, Marie-Fréderique Gauthier, François Julien, Laurent Biertho, Marie-Claude Vohl, André Tchernof","doi":"10.1152/ajpendo.00512.2024","DOIUrl":"10.1152/ajpendo.00512.2024","url":null,"abstract":"<p><p>Adipose tissue androgen turnover, dictated at least in part by the enzymes aldo-keto reductase 1 C type 2 (AKR1C2) and aldo-keto reductase 1 C type 3 (AKR1C3), has been linked to abdominal obesity. Recently, we investigated a single-nucleotide polymorphism (SNP) named rs28571858, that might increase <i>AKR1C2</i> and <i>AKR1C3</i> expression in human adipose tissue. Here, we studied the impact of rs28571848 on adipose tissue function and cardiometabolic health in bariatric surgery candidates. We genotyped a sample of 2,776 bariatric surgery candidates and retrospectively obtained anthropometry, blood lipid and glucose profiles, menopausal status, and medication use. In a subsample of 135 individuals (62% women, age 42 yr, body mass index of 51 kg/m²), we additionally assessed <i>AKR1C2</i> and <i>AKR1C3</i> expression in whole tissue by RT-qPCR. Features of adipose tissue dysfunction, such as mean adipocyte diameter and pericellular fibrosis, were assessed by histological staining and semiautomated image analysis. Finally, adipose tissue AKR1C family enzyme activity was measured by fluorimetry. The rs28571848 SNP affected <i>AKR1C3</i> expression in both subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in women only, while not altering <i>AKR1C2</i> expression in either men or women. Individuals carrying the minor allele exhibited increased VAT AKR1C activity compared to those with the wildtype genotype. Analysis of blood lipid profile in the whole cohort revealed that \"TT\" carriers had elevated total cholesterol, low-density lipoprotein-cholesterol, and indices of insulin resistance. The rs28571858 SNP increased adipose tissue <i>AKR1C3</i> expression and activity in women. Increased AKR1C3 may contribute to an adipose tissue milieu that prompts lipogenesis, adversely affecting cardiometabolic health by disrupting lipid homeostasis and insulin sensitivity.<b>NEW & NOTEWORTHY</b> rs28571858 has a minor allele frequency of 18.7% in a cohort of 2,776 residents of Quebec, Canada. rs28571858 is associated with adipose tissue <i>AKR1C3</i> expression and activity in women. Minor allele homozygote carriers have increased total cholesterol, LDL-cholesterol, and indices of insulin resistance.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E276-E286"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916296","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 attenuates polycystic ovary syndrome development via improved mitochondrial proteostasis.","authors":"Chaeyoung Shin, Li-Wei Chen, Md Nazmul Hossain, Xinrui Li, Sharmeen Islam, Zhongyun Kou, Qiaorong Cui, Jeanene Marie de Avila, Mei-Jun Zhu, Min Du","doi":"10.1152/ajpendo.00457.2025","DOIUrl":"10.1152/ajpendo.00457.2025","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder characterized by hyperandrogenism, inflammation, and ovarian dysfunction. Although exercise has been recognized as an effective nonpharmacological strategy for managing PCOS symptoms, the molecular mechanisms underlying its therapeutic benefits remain unclear. In this study, we used a dehydroepiandrosterone-induced PCOS mouse model to investigate how aerobic exercise ameliorates ovarian pathology. Our results demonstrated that exercise restored the estrous cycle, reduced ovarian cyst formation, and alleviated ovarian fibrosis and inflammation. Exercise upregulated ATP-dependent protease Lon peptidase 1 (LONP1) expression, accompanied by normalization of key steroidogenic protein levels, cytochrome P450 side-chain cleavage enzyme (CYP11A1), and steroidogenic acute regulatory protein (StAR). In parallel, exercise activated AMP-activated protein kinase (AMPK), which was accompanied by restoration of LONP1-associated mitochondrial proteolytic capacity and normalization of steroidogenic enzyme turnover. Exercise also enhanced mitochondrial biogenesis-related markers, including peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) and peroxisome proliferator-activated receptor-α (PPARα), suggesting improved mitochondrial homeostasis in the PCOS ovary.<b>NEW & NOTEWORTHY</b> This study identifies mitochondrial proteostasis as an important molecular mechanism underlying the beneficial effects of aerobic exercise in improving polycystic ovary syndrome (PCOS). Exercise attenuated PCOS development and pathology through normalizing steroidogenic enzyme degradation via LONP1 upregulation, suppressing ovarian inflammation and fibrosis, and activating mitochondrial biogenesis pathways. Although the beneficial effects of exercise on PCOS have been well recognized, this study reveals the mitochondrial proteostasis pathway underlying these preventive effects.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E390-E400"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12990670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146200021","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":"Umbilical cord plasma markers in gestational diabetes: evidence of fetal metaflammation, elevated GGT, and links to neonatal metabolic health.","authors":"Andreas Steiner, Anna Rieder, Jasmin Zaunschirm-Strutz, Elisa Weiss, Carolina Tocantins, Bettina Amtmann, Tarek Moustafa, Christina Stern, Azra Kulovic-Sissawo, Ursula Hiden","doi":"10.1152/ajpendo.00404.2025","DOIUrl":"10.1152/ajpendo.00404.2025","url":null,"abstract":"<p><p>Gestational diabetes mellitus (GDM) is a form of glucose intolerance that develops during pregnancy, affecting approximately 14% of pregnancies worldwide. GDM leads to an excess supply of nutrients to the fetus, influencing fetal metabolism and potentially stimulating metabolic inflammation (metaflammation), which may impact liver function. In fact, increased fetal liver size has been reported in GDM pregnancies. This study investigated the impact of GDM on fetal metaflammation and its potential association with the liver function parameters γ-glutamyl transferase (GGT), alanine transaminase (ALT), and bilirubin, in umbilical cord plasma (UCP). UCP samples were collected following healthy (<i>n</i> = 57) and GDM pregnancies (<i>n</i> = 25). Glucometabolic and lipid profiles, inflammatory markers, and liver function parameters were analyzed and the impact of GDM and the interrelation of liver biomarkers with maternal and neonatal parameters were assessed. UCP from GDM pregnancies exhibited increased levels of metaflammation-associated markers, including triglycerides, interleukin-6 and C-reactive protein (CRP). Among liver parameters, the detoxification and antioxidant defense enzyme GGT was elevated, whereas ALT and bilirubin species remained unchanged. Correlation analysis revealed that although GGT was increased in GDM, it was associated with improved metabolic characteristics, including reduced insulin resistance, insulin, C-peptide, and leptin, and increased high-density lipoprotein. Overall, these findings indicate that the GDM environment shifts fetal metabolism toward metaflammation and elevates GGT, an enzyme involved in detoxification and protection against oxidative stress. The inverse association of GGT with insulin resistance suggests a compensatory role of GGT, potentially mitigating fetal metabolic and inflammatory disturbances in GDM through its antioxidant activity.<b>NEW & NOTEWORTHY</b> Excess fetal nutrient supply in gestational diabetes mellitus (GDM) results in signs of fetal metabolic inflammation (metaflammation) in umbilical cord plasma, and higher levels of γ-glutamyl transferase (GGT), a liver enzyme involved in defense against oxidative stress. The correlations of GGT levels with reduced insulin resistance, C-peptide, and leptin suggest that GGT has a positive effect on fetal metabolic health.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E369-E379"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117624","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":"The important role of fatty infiltration of skeletal muscle in aging: skeletal muscle function, pathological mechanisms, and intervention.","authors":"Mei Yang, Fangli Zhou, Cui Wang, Ting Sun, Wanyu Zhao, Lu Liu, Yang Meng, Li Tian","doi":"10.1152/ajpendo.00473.2025","DOIUrl":"10.1152/ajpendo.00473.2025","url":null,"abstract":"<p><p>This review explores the various biological changes that occur during the aging process, elucidating the fundamental pathological mechanisms leading to a decline in muscle integrity and functionality. A primary focus of the review is the occurrence of fat infiltration within skeletal muscle, a phenomenon that becomes increasingly prevalent with advancing age. This study assesses the implications of fat infiltration on skeletal muscle performance, along with the regulatory signaling mechanisms potentially influenced by fat accumulation. Furthermore, it addresses a variety of intervention strategies aimed at alleviating these age-related changes, including nutritional supplements, exercise regimens, and pharmacological treatments. By integrating current findings in the field and addressing existing challenges, this review aims to conduct an in-depth exploration of the intricate connection between aging and skeletal muscle health, with the goal of guiding future research and clinical practices to improve the quality of life for older adults.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E309-E345"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145987598","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}