American journal of physiology. Endocrinology and metabolism最新文献

{"title":"Respiratory Resilience as Form Fades: Skeletal Muscle Mitochondrial Adaptation in Aging.","authors":"John Noone","doi":"10.1152/ajpendo.00369.2025","DOIUrl":"10.1152/ajpendo.00369.2025","url":null,"abstract":"","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939081","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":"Defective medium-chain fatty acid β-oxidation in the liver alters the fat preference and induces hepatic steatosis and glucose intolerance.","authors":"Tsugunori Maruyama, Sho Matsui, Satoshi Tsuzuki, Takahiro Horie, Koh Ono, Tsutomu Sasaki","doi":"10.1152/ajpendo.00276.2025","DOIUrl":"https://doi.org/10.1152/ajpendo.00276.2025","url":null,"abstract":"<p><p>Long-chain triglycerides (LCTs) exert obesogenic effects, whereas medium-chain triglycerides (MCTs) exert antiobesity effects. To date, most studies examining the distinct effects of MCTs and LCTs have been conducted under extreme conditions using high-fat diets (45-60 kcal% fat). In this study, we aimed to investigate the health effects of varying MCT/LCT intake ratios in 30 kcal% high-fat diets, using liver-specific medium-chain acyl-CoA dehydrogenase (MCAD)-deficient (MCAD^L-/-) mice. Since this fat level more closely resembles the human diet without causing overeating, it allows for a purer assessment of the metabolic effects of the MCT/LCT intake ratios compared with the results of studies using extreme high-fat conditions. We fed MCAD^L-/- mice 30 kcal% fat MCT and LCT diets for 12 wk. Notably, MCAD^L-/- mice consumed the LCT diet more than the MCT diet, without any difference in the total caloric intake. Despite no difference in body weight, MCAD^L-/- mice exhibited impaired glucose tolerance and elevated hepatic triacylglycerol and cholesterol levels. Moreover, lipid droplet size and gene expression levels of some inflammatory markers increased in the adipose tissues of MCAD^L-/- mice. Overall, these results suggest that the intact metabolism of medium-chain fatty acids in the liver is crucial for dietary fat preference regulation. Furthermore, antiobesity effects of MCTs are observed even when the percentage of MCT intake is increased without altering the total fat intake.<b>NEW & NOTEWORTHY</b> Medium-chain triglycerides (MCTs) exert antiobesity effects; however, whether these antiobesity effects are observed when the MCT/long-chain triglyceride intake is altered using a high-fat diet (30 kcal% fat) remains unclear. This study found that impaired medium-chain fatty acid metabolism in the liver reduced MCT preference, without altering the total fat intake, resulting in metabolic dysfunction. Therefore, increasing the MCT ratio in dietary fats possibly reduces the risk of obesity.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":"329 3","pages":"E433-E440"},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939052","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":"Sex-specific difference in intestinal glucose metabolism is associated with sexually dimorphic postprandial lactate shuttle and glucose homeostasis in mice.","authors":"Shuo Wang, Xinhui Zhang, Lingling Zhang, Shixuan Zhuo, Yan Chen","doi":"10.1152/ajpendo.00096.2025","DOIUrl":"10.1152/ajpendo.00096.2025","url":null,"abstract":"<p><p>Sexual dimorphism in glucose metabolism is increasingly recognized as a critical factor in metabolic homeostasis. Our prior study has highlighted the role of intestinal monocarboxylate transporter 1 (MCT1) in mediating lactate transport and its sex-specific effect on glucose metabolism in mice. Here, we investigated the sex-specific metabolic flux in the intestine and its impact on postprandial lactate shuttle and glucose homeostasis. Using a combination of isotopic tracing techniques and in vivo experiments, we discovered that intestinal epithelium exhibits sex-specific metabolic profiles, leading to differential glucose metabolism. Female mice displayed higher oxidative phosphorylation activity and greater utilization of lactate/pyruvate in the tricarboxylic acid (TCA) cycle than male mice, resulting in improved glucose tolerance. In contrast, male mice exhibited higher glycolytic activity with an increased postprandial lactate level, correlating with poorer glucose tolerance than female mice. Estrogen treatment in male mice reduced intestinal interstitial lactate level and improved glucose tolerance. Castration of male mice also improved glucose tolerance, whereas androgen replacement reversed this effect. Conversely, ovariectomy in female mice impaired glucose tolerance, which was restored by estrogen replacement. Our findings thus underscore the importance of sex-specific glucose metabolism in the intestine and its implications for metabolic health, laying a foundation for developing sex-specific therapeutic strategies for metabolic disorders.<b>NEW & NOTEWORTHY</b> Sex dimorphic difference in glucose homeostasis has been well recognized; however, how glucose metabolism in the intestine contributes to this phenomenon is poorly known. We discovered that the male mice have an elevated rate of glycolysis in the intestine, whereas the female mice have an increased rate of oxidative phosphorylation, contributing to the sex difference in glucose tolerance. In addition, sex hormones are crucial in mediating such a difference between the two sexes.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E393-E404"},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717290","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":"Metformin suppresses atherosclerosis by dampening extramedullary myelopoiesis.","authors":"Man K S Lee, Olivia D Cooney, Yifei Zhu, Yiyu Zhang, Xuzhu Lin, Danise-Ann Onda, Sandra Galic, Bruce E Kemp, Andrew J Murphy, Kim Loh","doi":"10.1152/ajpendo.00056.2025","DOIUrl":"10.1152/ajpendo.00056.2025","url":null,"abstract":"<p><p>Impaired cholesterol homeostasis is a major factor contributing to the development and progression of atherosclerosis. Previous studies have shown that metformin, the first-line antidiabetic therapy, has cardioprotective effects in patients with diabetes. However, the antiatherogenic effect of metformin in nondiabetic individuals remains unclear. The aim of this study was to determine the antiatherosclerotic effects of metformin under normoglycemic conditions and, mechanistically, to assess its impact on hematopoietic stem and progenitor cell (HSPC) biology and extramedullary myelopoiesis. Here, we demonstrated that metformin decreased atherosclerotic lesion size, reduced plaque macrophages, and lowered circulating atherogenic Ly6-C^hi monocytes and neutrophil levels in <i>Apoe</i>^-/- mice, independent of blood glucose regulation. Mechanistically, metformin-treated <i>Apoe</i>^-/- mice exhibited increased HSPC retention in the bone marrow and decreased numbers of circulating hematopoietic stem and progenitor cells (HSPCs), along with reduced levels of Ly6-C^hi monocytes and neutrophils in the spleen. Our results indicate that decreased circulating cholesterol and increased expression of the ATP-binding cassette transporter gene <i>Abca1</i> in HSPCs, thereby promoting cholesterol efflux in these cells, are critical factors leading to the suppressed mobilization of HSPCs and myelopoiesis in metformin-treated mice. Collectively, our findings support the use of metformin as an antiatherosclerotic agent under euglycemic conditions. We reveal that this effect is achieved by dampening HSPC mobilization and extramedullary myelopoiesis, providing molecular evidence for metformin's role in reducing macrophage-driven inflammation and, consequently, attenuating atherosclerotic progression.<b>NEW & NOTEWORTHY</b> This study uncovers a novel role for metformin in reducing inflammatory and atherogenic monocytes by dampening extramedullary myelopoiesis, thereby delaying atherosclerosis development under normoglycemic conditions. We demonstrate that metformin suppresses hematopoietic stem and progenitor cell mobilization and reduces macrophage-driven inflammation, providing mechanistic evidence for its antiatherosclerotic potential beyond diabetes management. These findings highlight new therapeutic opportunities for metformin in cardiovascular disease, extending its clinical utility to the prevention of atherosclerosis in nondiabetic individuals.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E420-E432"},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783220","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":"New insights into lactate in exercise adaptations: does protein lactylation play a role?","authors":"Zhen Wang, Lin Zhu","doi":"10.1152/ajpendo.00225.2025","DOIUrl":"10.1152/ajpendo.00225.2025","url":null,"abstract":"<p><p>Physical activity and exercise are widely recognized as effective ways to promote physical fitness and prevent disease; however, their underlying molecular mechanisms remain to be fully elucidated. Within the last few years, the discovery of lactylation has propelled the well-known exercise metabolite lactate into the scientific spotlight. As the end product of glycolysis, lactate was initially considered to be a \"metabolic waste\" leading to muscle fatigue; however, subsequent studies have demonstrated the importance of lactate as an energy substrate and a signal transduction molecule to coordinate various physiological processes. Importantly, the novel posttranslational modification, lactylation, establishes a bridge between lactate and epigenetics, and provides new perspectives for understanding the role of lactate in exercise-mediated health promotion. Although some recent evidence in rodents suggests that exercise increases protein lactylation, there are mixed findings in this area, with limited human studies showing no effects. This review summarizes current knowledge of exercise-mediated lactylation, why mixed findings in the literature may exist, and suggests future research that can add further clarity to this area of molecular biology.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E405-E419"},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820363","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":"Early complete weaning in mice induces hepatic steatosis, which is associated with changes in phospholipids, metabolites, gene expression, and epigenome.","authors":"Haruka Adachi, Shiori Ishiyama, Kentaro Yoshimura, Hirotake Kasai, Kazuki Mochizuki","doi":"10.1152/ajpendo.00184.2025","DOIUrl":"10.1152/ajpendo.00184.2025","url":null,"abstract":"<p><p>Early complete weaning may increase the risk of developing metabolic diseases. This study investigated whether early complete weaning in mice leads to the development of steatosis. Institute of Cancer Research (ICR) mouse male pups were weaned at 17 days [early complete weaning (EW)] or 21 days [normal complete weaning (NW)] and subsequently fed the AIN93G diet until 32 weeks of age. We measured the diameter of lipid droplets, primary metabolites, protein expression related to phospholipid synthesis, and histone modifications of the <i>Pemt</i> in the liver. The lipid droplet diameter was larger in EW mice than in NW mice. A set of phosphatidylcholine (PC) species, particularly PC(38:6), demonstrated lower mRNA and protein expression of <i>Pemt</i> and methylenetetrahydrofolate reductase, as well as decreased primary metabolites related to <i>S</i>-adenosylmethionine/choline, and a reduction in an antioxidative marker in EW mice. Moreover, histone methylation (H3K4 tri-methyl and H3K36 di-/tri-methyl) and acetylation around <i>Pemt</i> were also lower in these mice. The steatosis development due to early complete weaning in mice is closely and positively associated with a reduced amount of PC.<b>NEW & NOTEWORTHY</b> The development of steatosis due to early complete weaning in mice is closely positively associated with a reduced amount of PC and related metabolites, transcriptome changes including <i>Pemt</i>, and alterations in histone modifications around <i>Pemt.</i></p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E455-E462"},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726520","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":"Hyperglycemia worsens gut bacterial infection through intestinal Wnt, but independent of endotoxemia or obesity.","authors":"Arshpreet Bhatwa, Trevor C Lau, Joseph B McPhee, Fernando F Anhê, Gabriel F Anhê, Han Fang, Nicole G Barra, Yujin Li, Brittany M Duggan, Darryl Y Chan, Elizabeth Gunn, Claudia Gagnon, André Tchernof, André Marette, Katherine M Morrison, Brian K Coombes, Jonathan D Schertzer","doi":"10.1152/ajpendo.00251.2025","DOIUrl":"10.1152/ajpendo.00251.2025","url":null,"abstract":"<p><p>Obesity and diabetes are interlinked diseases, but it was unclear how obesity vs. diabetes modifies the risk and severity of gut bacterial infection. We aimed to determine how obesity or hyperglycemia, indicative of diabetes, altered metabolic endotoxemia and severity of enteric infection. Metabolic endotoxemia was determined using TLR4 activity reporter assay in serum from humans with obesity or diabetes, and from hyperglycemic <i>Akita</i>^+/- mice and genetically obese <i>ob/ob</i> mice. Diarrhea severity during <i>Escherichia coli</i> infection was determined in humans during a previous community outbreak. The enteropathogen <i>Citrobacter rodentium</i> was used to define the mechanisms of action that altered the severity of enteric infection in <i>ob/ob</i> and <i>Akita</i>^+/- mice. We found that elevated blood glucose, indicative of diabetes, was associated with increased occurrence and severity of diarrhea during an <i>E. coli</i> outbreak in humans. Metabolic endotoxemia occurred in a separate cohort of people with obesity who were normoglycemic or hyperglycemic, and in mice with either obesity or hyperglycemia. Hyperglycemia, not obesity, increased mortality during infection with the diarrhea-causing pathogen <i>C. rodentium</i> in mouse models of type 1 and type 2 diabetes. Common indicators of poor prognosis, such as gut pathology, systemic bacteraemia, or metabolic endotoxemia, did not predict worse outcomes during enteric infection in diabetic mice. Hyperglycemia activated intestinal Wnt/β-catenin and increased mortality, which could be reversed by blocking Wnt/β-catenin, lowering blood glucose, or restoring fluid balance during infection. The increased severity of infection via overactivation of intestinal Wnt/β-catenin during hyperglycemia may be a potential target for therapeutics.<b>NEW & NOTEWORTHY</b> We show that elevated blood glucose is associated with worse diarrhea during an <i>Escherichia coli</i> outbreak in humans. Obesity or hyperglycemia was sufficient to promote metabolic endotoxemia in humans and mice. Hyperglycemia promotes worse enteric infection outcomes independent of obesity. Finally, we showed that blocking of Wnt/β-catenin, lowering blood glucose, or restoring fluids improved enteric infection outcomes in hyperglycemic mice.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E441-E454"},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870871","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":"Lipidome profile of Cystic Fibrosis Related Diabetes, Type 1 and Type 2 Diabetes Mellitus: potential links to inflammation and glucose and lipid metabolism.","authors":"Alessandra Mingione, Cristian Loretelli, Michele Dei Cas, Francesca Pivari, Matteo Barcella, Ivan Merelli, Aida Zulueta, Rita Paroni, Letizia Corinna Morlacchi, Valentina Vaira, Francesca Gillani, Marco Piccoli, Luigi Anastasia, Elisabetta Albi, Ilaria Righi, Mario Nosotti, Paolo Fiorina, Anna Caretti, Lorenzo Rosso, Franco Folli, Paola Signorelli","doi":"10.1152/ajpendo.00293.2024","DOIUrl":"https://doi.org/10.1152/ajpendo.00293.2024","url":null,"abstract":"<p><p>Cystic Fibrosis (CF) is a genetic disease that primarily affects the pancreas and lungs. CF dyslipidaemia is characterized by decreased circulating lipids and increased ectopic lipid deposition in liver, pancreas, and lungs. Pancreatic exocrine insufficiency precedes the onset of CF related diabetes (CFRD). We hypothesized that different mechanisms contribute to CFRD development and progression, including features of Type 1 and Type 2 diabetes mellitus (T1DM and T2DM). Thus, we compared their plasma inflammatory, metabolic/hormonal, and lipidomic profiles, using Luminex assays and untargeted mass spectrometry analyses. Then, we compared the lipidomic profiles of lung biopsies and plasma extracellular vesicles (EVs) of CFRD and patients with other lung diseases (LD). Inflammatory cytokines (IL6 and IL1β) and chemokines (IL8 and MCP-1) were increased in the plasma of CFRD as compared with T1DM, whereas only cytokines increased when comparing with T2DM. Low insulin and C-peptide characterized CFRD and T1DM. Phosphatidylcholine, phosphatidylethanolamine and storage lipids were reduced and free fatty acids (FA) were increased in CFRD plasma compared with T1DM and T2DM. When comparing CFRD with LD, systemic inflammation was increased to a similar extent. Increased levels of sphingolipids, glycerolipids, acylcarnitines were found in lung biopsies of CFRD as compared to LD. Increased triacylglycerols in lung biopsies positively correlated with lung inflammatory infiltrates (CD68 positive cells) of CFRD patients. In conclusion, CFRD is characterized by altered lipid metabolism, insulin deficiency and insulin resistance, partially overlapping with both T1DM and T2DM. CFRD also involves ectopic lung lipids accumulation correlating with increased <i>in situ</i> inflammation.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939043","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":"PD-1-Ab therapeutic hypothyroidism associated with decreased of peripheral blood CD4⁺ T cells and addressed prophylactic medication of thyroxine administration.","authors":"Linyao Lu, Congcong Li, Wei Wei, Guanghui Ma, Xinna Zhou, Xiaoli Wang, Shuang Wang, Jun Ren","doi":"10.1152/ajpendo.00192.2025","DOIUrl":"https://doi.org/10.1152/ajpendo.00192.2025","url":null,"abstract":"<p><p><b>Background:</b> Immune checkpoint inhibitor PD-1 antibody (PD-1-Ab) has arisen the increasing clinical prevalence of immune-related adverse events (irAEs) such as hypothyroidism. Hypothyroidism is the common irAEs but the mechanism of such immunological pathogenesis was still unclear. <b>Methods:</b> We have developed an unique hypothyroidism mice model induced by mimicking clinical exposure to PD-1-Ab. Then we analyzed the immune cell phenotypes in the peripheral blood of mouse models by flow cytometry and further verified in patients' samples. Therefore we have further investigated the molecular pathogenesis of such condition through the spatial transcriptome sequencing in thyroid glands. Those findings have supported the recommendations of prophylactic treatment with thyroxine in a very beginning time-point. <b>Results:</b> The results showed that the CD4⁺ T cell subset declined in the peripheral blood of hypothyroidism mice induced by PD-1-Ab, which was consistent with the similarities in the hypothyroidism patients. Moreover, spatial transcriptome sequencing of thyroid glands of mice was predominantly featured by up-regulated IL-17 signaling pathway and involved endoplasmic reticulum stress, which provided the evidences to address the preliminary roles of immunological pathogenesis participated. In addition, we have demonstrated that a combination with early onset of thyroxine supplements could prevent the subsequent occurrence of hypothyroidism. <b>Conclusions:</b> Those experimental and clinical data provided the awareness that CD4⁺ T cells are associated with hypothyroidism caused by PD-1-Ab and therefore prophylactic administration of thyroxine should be considered with great caution and in timely manner.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939065","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":"Modulation of peripheral energy metabolism through central leucine administration in rainbow trout (<i>Oncorhynchus mykiss</i>).","authors":"Sara Comesaña, Gabriel Pérez-Tierra, Jessica Calo, Cristina Velasco, Marta Conde-Sieira, José L Soengas","doi":"10.1152/ajpendo.00066.2025","DOIUrl":"10.1152/ajpendo.00066.2025","url":null,"abstract":"<p><p>We aimed to evaluate the role of central leucine administration in the modulation of peripheral energy metabolism in fish. For this, rainbow trout (<i>Oncorhynchus mykiss</i>) were administered via intracerebroventricular 1 μL·100 g^-1 body mass of saline solution alone (Control) or containing 10 μg·μL^-1 of leucine. Samples of plasma, liver, adipose tissue, white muscle, and red muscle were collected 1- and 3-h postinjection. Firstly, metabolite levels were assessed in plasma and liver and a decrease in liver triglyceride at 1 h and an increase in plasma fatty acid at 3 h were observed. Metabolites levels were also assessed in white muscle, revealing decreased levels of α-amino acids and glycogen at 1 h. In addition, liver enzymatic activity and mRNA levels related to glucose, fatty acid, and amino acid metabolism showed no relevant changes. Then, energy metabolism in adipose tissue and muscle was assessed by examining the mRNA abundance of genes related to metabolism and oxidative capacity, thermogenesis, mitochondrial dynamics (mitochondrial fusion and fission), and other metabolic regulatory factors. Mitochondrial fusion was significantly influenced at 1-h postinjection in white muscle (upregulation of <i>mfn1</i>, <i>mfn2</i>, <i>tfam</i>, and <i>opa1</i>) and to a lesser extent in red muscle (upregulation of <i>tfam</i>). These findings differ from studies in mammals with leucine and in fish with other nutrients, in which liver metabolism is modulated. This also highlights the importance of leucine and its relationship with muscle and mitochondrial dynamics in controlling energy homeostasis in fish.<b>NEW & NOTEWORTHY</b> We studied how central leucine administration affects peripheral energy metabolism in rainbow trout. No significant changes were found in liver metabolism, differing from mammalian comparable studies and from changes in hypothalamic energy status elicited by other nutrients in fish. Mitochondrial fusion was notably influenced in white muscle and to a lesser extent in red muscle. These findings highlight the unique role of leucine in the maintenance of energy homeostasis in fish.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E314-E323"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615832","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}