American journal of physiology. Endocrinology and metabolism最新文献

{"title":"Corrigendum for Galsgaard et al., volume 328, 2025, p. E435-E446.","authors":"","doi":"10.1152/ajendo.00437.2024_COR","DOIUrl":"https://doi.org/10.1152/ajendo.00437.2024_COR","url":null,"abstract":"","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":"328 4","pages":"E652"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802248","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 evolution of steatosis and fibrosis in mice on a MASH-inducing diet and the effects of housing temperature.","authors":"Neil B Blok, Andriy Myronovych, Garrett McMahon, Nadejda Bozadjieva-Kramer, Randy J Seeley","doi":"10.1152/ajpendo.00401.2024","DOIUrl":"10.1152/ajpendo.00401.2024","url":null,"abstract":"<p><p>Obesity induction in mice requires high-fat diet exposure. Although hepatic steatosis develops, progression to inflammation and fibrosis, as in humans, requires prolonged exposure and additional dietary factors. Immunosuppression at room temperature may slow this progression. We evaluated thermoneutrality's effect on metabolic dysfunction-associated steatohepatitis (MASH) development using a fibrosis-inducing MASH [Gubra-Amylin NASH (GAN)] diet. Mice were fed either a MASH or chow diet and housed at room temperature or thermoneutrality. MASH diet groups were euthanized monthly from 4 to 7 mo. Serum markers of hepatic function were analyzed, and liver histology assessed steatosis, inflammation, ballooning [nonalcoholic fatty liver disease activity score (NAS) score], and fibrosis via Picrosirius Red staining. MASH diet increased body weight, liver-to-body mass ratio, and hepatic fat, with no difference between housing conditions. Housing temperature had minimal effects on MASH. Serum markers and hepatic fibrosis were similar across groups. NAS score was lower at 4 mo in thermoneutral MASH mice but not by 7 mo. Thermoneutrality did not significantly impact MASH development. These findings, alongside existing literature, suggest thermoneutral housing does not consistently enhance MASH progression in GAN MASH-fed mice.<b>NEW & NOTEWORTHY</b> The development of MASH in mice-does housing temperature make a real difference?</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E513-E523"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490535","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":"Dehydration-induced AVP stimulates glucagon release and ketogenesis.","authors":"Thomas G Hill, Linford J B Briant, Angela Kim, Yanling Wu, Patrik Rorsman, Ingrid Wernstedt Asterholm, Anna Benrick","doi":"10.1152/ajpendo.00505.2024","DOIUrl":"10.1152/ajpendo.00505.2024","url":null,"abstract":"<p><p>Gliflozins, such as dapagliflozin, belong to a class of drugs that inhibit the sodium-glucose cotransporter 2. Gliflozins have been found to raise glucagon levels, a hormone secreted from pancreatic islet α-cells, which can trigger ketosis. However, the precise mechanisms through which gliflozins increase glucagon secretion remain poorly understood. In addition, gliflozins induce osmotic diuresis, resulting in increased urine volume and plasma osmolality. In this study, we investigated the hypothesis that a compensatory increase in arginine-vasopressin (AVP) mediates dapagliflozin-induced increases in glucagon in vivo. We show that dapagliflozin does not increase glucagon secretion in the perfused mouse pancreas, neither at clinical nor at supra-clinical doses. In contrast, AVP potently increases glucagon secretion. In vivo, dapagliflozin increased plasma glucagon, osmolality, and AVP. An oral load with hypertonic saline amplified dapagliflozin-induced glucagon secretion. Notably, a similar increase in glucagon could also be elicited by dehydration, evoked by 24-h water restriction. Conversely, blockade of vasopressin 1b receptor signaling, with either pharmacological antagonism or knockout of the receptor, resulted in reduced dapagliflozin-induced glucagon secretion in response to both dapagliflozin and dehydration. Finally, blocking vasopressin 1b receptor signaling in a mouse model of type 1 diabetes diminished the glucagon-promoting and ketogenic effects of dapagliflozin. Collectively, our data suggest that AVP is an important regulator of glucagon release during both drug-induced and physiological dehydration.<b>NEW & NOTEWORTHY</b> Gliflozin-induced ketogenic effects partly result from increased glucagon levels. This study shows that dapagliflozin-triggered glucagon secretion is not directly mediated by the pancreas but rather linked to arginine-vasopressin (AVP). Dehydration, common in diabetic ketoacidosis, elevates AVP, potentially explaining the increased ketoacidosis risk in gliflozin-treated patients. Thus, our results highlight AVP as a potential therapeutic target to mitigate the risk of ketoacidosis associated with gliflozin treatments in patients with diabetes.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E633-E644"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656039","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":"A specific metabolomic and lipidomic signature reveals the postpartum resolution of gestational diabetes mellitus or its evolution to type 2 diabetes in rat.","authors":"Paul Bobin, Delphine Mitanchez, Blandine Castellano, Isabelle Grit, Thomas Moyon, Axel Raux, Anne Vambergue, Norbert Winer, Dominique Darmaun, Catherine Michel, Gwenola Le Drean, Marie-Cécile Alexandre-Gouabau","doi":"10.1152/ajpendo.00396.2024","DOIUrl":"10.1152/ajpendo.00396.2024","url":null,"abstract":"<p><p>Gestational diabetes mellitus (GDM) represents a major public health concern due to adverse maternal postpartum and long-term outcomes. Current strategies to manage GDM fail to reduce the maternal risk to develop later impaired glucose tolerance (IGT) and type 2 diabetes (T2D). In a rodent model of diet-induced GDM without obesity, we explored the perinatal metabolic adaptations in dams with gestational IGT followed by either persistent or resolved postpartum IGT. Female Sprague-Dawley rats were fed a high-fat high-sucrose (HFHS) or a chow [control group (CTL)] diet, 1 wk before mating and throughout gestation (G). Following parturition, HFHS dams were randomized to two subgroups: one switched to a chow diet and the other one maintained on an HFHS diet throughout lactation (L). Oral glucose tolerance tests (OGTTs) were performed, and plasma metabolome-lipidome were characterized at G12 and L12. We found that <i>1</i>) in GDM-pregnant dams, IGT was associated with incomplete fatty acid oxidation (FAO), enhanced gluconeogenesis, altered insulin signaling, and oxidative stress; <i>2</i>) improved glucose tolerance postpartum seemed to restore complete FAO along with elevation of nervonic acid-containing sphingomyelins, assumed to impart β-cell protection; and <i>3</i>) persistence of IGT after delivery was associated with metabolites known to predict the early onset of insulin and leptin resistance, with maintained liver dysfunction. Our findings shed light on the impact of postpartum IGT evolution on maternal metabolic outcome after an episode of GDM. They suggest innovative strategies, implemented shortly after delivery and targeted on these biomarkers, should be explored to curb or delay the transition from GDM to T2D in these mothers.<b>NEW & NOTEWORTHY</b> Specific metabolomic/lipidomic features are associated with GDM postpartum outcomes. GDM-pregnant dams exhibit partial fatty acid oxidation and boosted gluconeogenesis. Resolution of postpartum IGT relies on nervonic acid-sphingomyelin, a β-cell protector. Postpartum IGT persistence suggests muscle insulin resistance and liver dysfunction.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E493-E512"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412968","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":"Mammary tumor development induces perturbation of liver glucose metabolism with inflammation and fibrosis.","authors":"Anouk Charlot, Anthony Bringolf, Joris Mallard, Amélie Jaulin, Emilie Crouchet, Anne-Laure Charles, Delphine Duteil, Fabien Alpy, Catherine-Laure Tomasetto, Thomas F Baumert, Joffrey Zoll","doi":"10.1152/ajpendo.00498.2024","DOIUrl":"10.1152/ajpendo.00498.2024","url":null,"abstract":"<p><p>Cancer cells rely on glycolysis and lactic fermentation for ATP production, inducing an abnormal glucose uptake in tumors. However, it is largely unknown whether the increased tumor glucose consumption affects overall body glucose homeostasis including perturbation of the liver glucose production pathways. The effect of mammary tumor development on the liver metabolism pathway was examined by using a mouse model based on FVB/N wild-type (WT-SD) and FVB/N-Tg(MMTV-PyVT)634Mul/J mice (Tg-SD), who develop spontaneous mammary tumors. Blood and livers were analyzed for metabolic changes, by measuring histological staining, signaling, and insulin sensitivity. Tg-SD mice developed mammary tumors with an average weight of 6 g, and cancer development increased total food intake without impacting body weight gain. Tumor development did not affect blood glycemia and lactate levels but increased insulin and homeostasis model assessment of insulin resistance (HOMA-IR) index (<i>P</i> = 0.06). In the liver, Tg-SD mice with tumors exhibited a decrease in glycogen content and an increase in gluconeogenesis gene expression, as G6pc, Pgc1α, and Foxo1 (<i>P</i> < 0.05), as well as Pepck and Ldha (<i>P</i> < 0.01). Moreover, the phosphorylation of AMPK and AKT was significantly decreased (<i>P</i> < 0.01 and <i>P</i> < 0.05, respectively). Surprisingly, liver fibrosis was markedly increased in Tg mice (<i>P</i> < 0.05) alongside elevated inflammatory gene expression, such as IL1β (<i>P</i> < 0.01) or IL6 (<i>P</i> < 0.05). Here, we found that the development of non-metastatic mammary tumors using the MMTV-PyMT mouse model disrupts liver function through the development of inflammation, fibrosis, and metabolic perturbation, including an increase in glucose production and insulin resistance. Finally, these observations unravel a previously unknown metabolic cross talk between the tumors and the liver.<b>NEW & NOTEWORTHY</b> This work demonstrates that the spontaneous development of non-metastatic mammary tumors triggers hepatic activation of endogenous glucose production pathways, coinciding with the onset of insulin resistance. This finding suggests a significant cross talk between tumors and the liver during tumorigenesis, aiming at enhancing glucose production to meet the elevated energy demands of the tumor. Understanding this interaction could provide insights into metabolic alterations associated with cancer and lead to potential therapeutic targets to inhibit tumor metabolism.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E645-E651"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662039","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":"Plasma complement system markers and their association with cardiometabolic risk factors: an ethnic comparison of White European and Black African men.","authors":"Reuben M Reed, Wioleta M Zelek, B Paul Morgan, Gráinne Whelehan, Sam Lockhart, Stephen O'Rahilly, Oliver C Witard, Martin B Whyte, Louise M Goff","doi":"10.1152/ajpendo.00419.2024","DOIUrl":"10.1152/ajpendo.00419.2024","url":null,"abstract":"<p><p>Populations of Black African (BA) ancestry are disproportionately affected by cardiometabolic diseases, possibly due to dysregulation of the complement system. This study aimed to determine relationships between fasting complement markers and cardiometabolic risk in BA and White European (WE) men, and whether postprandial complement response differs by ethnicity. Eighty-eight BA and 97 WE men [age = 44.4 (42.0-47.6) yr, body mass index (BMI) = 29.2 ± 4.5 kg·m^-2] were assessed for fasting plasma complement markers and cardiometabolic risk factors. A second cohort (<i>n</i> = 20 men, 10 BA) [age = 31.0 ± 1.1 yr, BMI = 27.1 (26.0-28.6) kg·m^-2] men underwent a moderate-to-high-fat feeding protocol to measure postprandial plasma complement, serum insulin, plasma glucose, triacylglycerol (TAG), and nonesterified fatty acids. C4 and Factor D were lower, and iC3b was higher in BA compared with WE men. C3 and C4 were strongly associated with all adiposity markers in both ethnicities, but the WE cohort showed stronger associations between C3 and subcutaneous adipose tissue, C5 and WC, and iC3b and visceral adipose tissue compared with BA. C3 was associated with all cardiometabolic risk factors in both ethnicities. Associations between C5 and cholesterol, C4 and TAG, and terminal complement complex and (both total and LDL)-cholesterol were only observed in the WE cohort. There was a trend toward ethnic differences in postprandial Factor D (<i>P</i> = 0.097) and iC3b (<i>P</i> = 0.085). The weaker associations between the complement system markers with adiposity and lipid profiles in BA compared with WE men suggest ethnic differences in the determinants of complement production and activation, whereby adipose tissue may play a less important role in BA men.<b>NEW & NOTEWORTHY</b> The present study found that markers of the complement system were less strongly associated with adiposity and lipid profiles in Black African men compared with White European men, suggesting ethnic differences in the determinants of complement production and activation. In Black African men, adipose tissue may play a less important role in complement production and activation and also in the link with traditional cardiometabolic risk factors.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E611-E619"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565782","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 metabolically protective energy expenditure increase of <i>Pik3r1</i>-related insulin resistance is not explained by Ucp1-mediated thermogenesis.","authors":"Ineke Luijten, Ami Onishi, Eleanor J McKay, Tore Bengtsson, Robert K Semple","doi":"10.1152/ajpendo.00449.2024","DOIUrl":"https://doi.org/10.1152/ajpendo.00449.2024","url":null,"abstract":"<p><p>Human SHORT syndrome is caused by dominant negative human PIK3R1 mutations that impair insulin-stimulated phosphoinositide 3-kinase (PI3K) activity. This produces severe insulin resistance (IR) and often reduced adiposity, commonly described as lipodystrophy. However unlike human primary lipodystrophies, SHORT syndrome does not feature fatty liver or dyslipidaemia. <i>Pik3r1^Y657*/WT</i> (Pik3r1^Y657*) mice metabolically phenocopy humans, moreover exhibiting increased energy expenditure on high fat feeding. We have hypothesised that this increased energy expenditure explains protection from lipotoxicity, and suggested that understanding its mechanism may offer novel approaches to mitigating the metabolic syndrome. We set out to determine whether increased Ucp1-dependent thermogenesis explains the increased energy expenditure in Pik3r1-related IR. Male and female Pik3r1^Y657* mice challenged with a 45% fat diet for 3 weeks at 21°C showed reduced metabolic efficiency not explained by changes in food intake or physical activity. No changes were seen in thermoregulation, assessed by thermal imaging and a modified Scholander protocol. Ucp1- dependent thermogenesis, assessed by norepinephrine-induced oxygen consumption, was also unaltered. Housing at 30°C did not alter the metabolic phenotype of male Pik3r1^Y657* mice, but led to lowered physical activity in female Pik3r1^Y657* mice compared to controls. Nevertheless these mice still exhibited increased energy expenditure. Ucp1-dependent thermogenic capacity at 30°C was similar in Pik3r1^Y657* and WT mice. We conclude that the likely metabolically protective 'energy leak' in Pik3r1-related IR is not caused by Ucp1- mediated BAT hyperactivation, nor impaired thermal insulation. Further metabolic studies are required to seek alternative explanations such as non Ucp1-mediated futile cycling.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727498","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":"GLP-1 receptor agonist exendin-4 suppresses food intake by inhibiting hindbrain orexigenic NPY neurons.","authors":"Jiayi Shen, Mengtian Wang, Guodong Pang, Yan Zhang, Jian Zhang, Yuyan Shi, Ji Liu, Cheng Zhan","doi":"10.1152/ajpendo.00528.2024","DOIUrl":"https://doi.org/10.1152/ajpendo.00528.2024","url":null,"abstract":"<p><p>Peripherally delivered glucagon-like peptide-1 (GLP-1)-based drugs suppress eating through their action in the brain. However, the specific neuronal mechanisms, especially their impacts on the orexigenic circuit, remain largely elusive. Neuropeptide Y (NPY) neurons in the nucleus tractus solitarius (NTS) are newly identified as orexigenic neurons with a potent eating-stimulating effect, but their responses to GLP-1 drugs are unknown. Through ex vivo electrophysiological recordings, we study the impacts of GLP-1 receptor (GLP-1R) agonist exendin-4 on NTS^NPY neurons. We discovered that the GLP-1R agonist exendin-4 inhibits NTS^NPY neuronal activity via GABA_b receptors by augmenting presynaptic GABA release. We also explored the contribution of NTS^NPY neurons to exendin-4-mediated eating suppression. Interestingly, chemogenetic activation of NTS^NPY neurons effectively counteracted exendin-4-induced anorexigenic effect. Moreover, chemogenetic inhibition of NTS^NPY neurons mimicked the eating-suppressing effect of exendin-4. Collectively, our findings highlight a population of orexigenic NTS^NPY neurons that may be targeted by a GLP-1R agonist to suppress food intake, suggesting that this neuronal population has translational importance as a potential therapeutic target for obesity treatment.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699378","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 choice of diet is determinative for the manifestation of UCP1-dependent diet-induced thermogenesis.","authors":"Raman Ahluwalia, Ineke H N Luijten, Celso P B Sousa-Filho, G Ruda F Braz, Natasa Petrovic, Irina G Shabalina, Barbara Cannon, Jan Nedergaard","doi":"10.1152/ajpendo.00038.2025","DOIUrl":"https://doi.org/10.1152/ajpendo.00038.2025","url":null,"abstract":"<p><p>The existence of the phenomenon of diet-induced thermogenesis - and its possible mediation by UCP1 in brown adipose tissue - has long been, and is presently, an important metabolic controversy. Particularly, several recent studies have failed to observe the hallmark of the phenomenon: augmentation of diet-induced obesity in UCP1-ablated mice, thus further casting doubt on the possible importance of this thermogenesis for human metabolic control. However, scrutiny of the experimental details revealed important procedural differences between experiments that did not or did show this augmentation of diet-induced obesity. Particularly, there were notable differences between the commercial diets used (Research-Diets or Ssniff). We therefore tested to what degree these differences would suffice to explain the absence of a UCP1 effect. Wildtype mice fed Research-Diets high-fat diet became obese but UCP1-ablated mice became even more obese, as expected if UCP1-dependent diet-induced thermogenesis exists. Mice fed the Ssniff high-fat diet became less obese than those on the Research-Diets food - and, importantly, no effect of UCP1 ablation was seen. The result with the Research-Diets diet was fully due to differences in total fat mass and not explainable by differences in food intake. The two diets are different in carbohydrate (sucrose) and lipid (lard versus palm oil) composition and in texture and taste. Probably some of these factors explain the difference but the important conclusion is that when an appropriate diet was offered, the body weight manifestation of UCP1-dependent diet-induced thermogenesis was a reproducible phenomenon that may have significance also for human metabolic control.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646955","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 alters molecular profiles of inflammation and substrate metabolism in human white adipose tissue.","authors":"Maria F Pino, Pieter Dijkstra, Katie L Whytock, Cheehoon Ahn, Gongxin Yu, James A Sanford, Josh Hansen, Chelsea Hutchinson, Marina Gritsenko, Paul Piehowski, Joshua N Adkins, Elvis A Carnero, Stuart Sealfon, Elena Zaslavsky, Venugopalan Nair, Steve R Smith, Lauren M Sparks","doi":"10.1152/ajpendo.00339.2024","DOIUrl":"10.1152/ajpendo.00339.2024","url":null,"abstract":"<p><p>White adipose tissue (WAT) plays a significant role in whole body energy homeostasis, and its excess typifies obesity. In addition to WAT quantity, perturbations in the basic cellular processes of WAT (i.e., quality) are also associated with obesity and metabolic disease. Exercise training alleviates metabolic perturbations associated with obesity; however, the underlying molecular mechanisms that drive these metabolic adaptations in WAT are not well described. Abdominal subcutaneous WAT biopsies were collected after an acute bout of exercise (1 day after) at baseline and following 3 wk of supervised aerobic training in sedentary overweight women (<i>n</i> = 6) without alterations in body weight and fat mass. RNA-seq, global proteomics, and phosphoproteomics in WAT revealed training-induced changes in 1,527 transcripts, 154 proteins, and 144 phosphosites, respectively. Training decreased abundance of transcripts and proteins involved in inflammation and components of the extracellular matrix and increased abundance of transcripts and proteins related to fatty acid esterification and lipolysis. In summary, short-term aerobic training significantly reduces local inflammation and increases lipid metabolism in WAT of sedentary overweight women-independent of alterations in body and fat mass. As such, some of the health benefits of aerobic training may occur through molecular alterations in WAT (i.e., enhanced quality) rather than a sheer reduction in WAT quantity.<b>NEW & NOTEWORTHY</b> This is the first study to utilize a multiomic (RNAseq, proteomics, and phosphoproteomics) approach to investigate molecular adaptations in WAT after a short-term intervention in sedentary overweight women. We show that supervised aerobic training reduces molecular markers of inflammation and proteins regulating ECM and increases abundance of transcripts and proteins involved in lipolysis and fatty acid re-esterification, indicating that molecular adaptations in WAT occur independent of alterations in body weight or fat mass.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E478-E492"},"PeriodicalIF":4.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397764","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}