American journal of physiology. Endocrinology and metabolism最新文献

{"title":"Induction of erythropoietin by dietary medium-chain triacylglycerol in humans.","authors":"Josephine M Kanta, Annemarie Lundsgaard, Amanda Schaufuss, Maximilian Kleinert, Bente Kiens, Andreas M Fritzen","doi":"10.1152/ajpendo.00415.2024","DOIUrl":"10.1152/ajpendo.00415.2024","url":null,"abstract":"<p><p>Erythropoietin (EPO) is pivotal in regulating red blood cell (erythrocyte) concentrations and is primarily synthesized in the kidney. Recent research has unveiled a possible link between elevated circulating concentrations of ketone bodies (KB) and circulating EPO concentrations; however, it is not known whether nutritionally induced endogenous ketogenesis can be a stimulus to induce EPO in humans. Therefore, this study aimed to assess whether acute and chronic intake of medium-chain fatty acid-containing triacylglycerol (MCT), which rapidly enhances endogenous circulating KB, would elevate circulating EPO concentrations in humans, as indicated by prior work with exogenous KB administration. The study followed a crossover design involving 16 young men undergoing two 8-day MCT or energy-matched long-chain fatty acid-containing triacylglycerol (LCT) interventions in a randomized order. Five-hour test days were performed before and after each intervention, in which circulating KB and EPO concentrations as well as hematological parameters were assessed. Acute intake of MCT yielded a 222% sustained 5-h elevation in KB concentrations compared with LCT-with notable peak values of 0.7 ± 0.1 mmol·L^-1 (312% above basal values). Remarkably, within just 8 days of daily MCT intake an impressive 38% increase in basal, fasting plasma EPO concentrations (7.19 ± 1.14 to 9.91 ± 1.25 mIU·mL^-1) was demonstrated. In conclusion, this study unveils a novel physiological stimulus of circulating EPO concentrations in humans, potentially offering a new dietary approach to counter anemia in cardiovascular diseases.<b>NEW & NOTEWORTHY</b> This study is the first to assess the effects of nutritionally induced ketogenesis by acute and subchronic intake of medium-chain fatty acids on plasma erythropoietin concentrations. Medium-chain fatty acid intake increases postprandial ketone body concentrations and within only 8 days of daily intake substantially enhances basal plasma erythropoietin concentrations in young men. We therefore reveal a dietary stimulus of endogenous circulating erythropoietin concentrations in humans, with the potential to counter anemia in cardiovascular diseases.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E210-E216"},"PeriodicalIF":4.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942656","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":"Neuroimmunometabolism: how metabolism orchestrates immune response in healthy and diseased brain.","authors":"Anil Kumar Rana, Babita Bhatt, Chitralekha Gusain, Surya Narayan Biswal, Debashree Das, Mohit Kumar","doi":"10.1152/ajpendo.00331.2024","DOIUrl":"10.1152/ajpendo.00331.2024","url":null,"abstract":"<p><p>Neuroimmunometabolism describes how neuroimmune cells, such as microglia, adapt their intracellular metabolic pathways to alter their immune functions in the central nervous system (CNS). Emerging evidence indicates that neurons also orchestrate the microglia-mediated immune response through neuro-immune cross talk, perhaps through metabolic signaling. However, little is known about how the brain's metabolic microenvironment and microglial intracellular metabolism orchestrate the neuroimmune response in healthy and diseased brains. This review addresses the balance of immunometabolic substrates in healthy and diseased brains, their metabolism by brain-resident microglia, and the potential impact of metabolic dysregulation of these substrates on the neuroimmune response and pathophysiology of psychiatric disorders. This review also suggests metabolic reprogramming of microglia as a preventive strategy for the management of neuroinflammation-related brain disorders, including psychiatric diseases.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E217-E229"},"PeriodicalIF":4.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942698","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":"Roux-en-Y gastric bypass alleviates kidney inflammation and improves kidney function in <i>db/db</i> mice by activating TLCA/TGR5 pathway.","authors":"Hongmei Lang, Jie Xiang, Xiaorong Chen, Dan Tong, Lijuan Wang, Aidi Mou, Daoyan Liu, Peng Gao, Zongshi Lu, Zhiming Zhu","doi":"10.1152/ajpendo.00248.2024","DOIUrl":"10.1152/ajpendo.00248.2024","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) is a severe diabetic microvascular complication featured by chronic low-grade inflammation. Roux-en-Y gastric bypass (RYGB) surgery has gained importance as a safe and effective surgery to treat DKD. Bile acids significantly change after RYGB, which brings a series of metabolic benefits, but the relationship with the improvement of DKD is unclear. Therefore, this study performed RYGB surgery on <i>db/db</i> mice to observe the beneficial effects of the surgery on the kidneys and performed bile acid-targeted metabolomics analysis to explore bile acid changes. We found that RYGB significantly reduced albuminuria in <i>db/db</i> mice, improved renal function, reversed renal structural lesions, and attenuated podocyte injury and inflammation. Notably, bile acid metabolomic analysis revealed taurolithocholic acid (TLCA) as the most significantly altered bile acid after RYGB. Furthermore, in vitro and in vivo validation experiments revealed that TLCA supplementation improved renal function and reduced renal inflammatory damage in <i>db/db</i> mice. In addition, TLCA inhibited high glucose-induced inflammatory damage in MPC-5 cells, and its mechanism of action may be related to activating Takeda G protein-coupled receptor 5 (TGR5), inhibiting NF-κB phosphorylation, and thus inhibiting inflammatory response. In conclusion, RYGB may play a protective role in the kidneys of diabetic mice by activating the TLCA/TGR5 pathway.<b>NEW & NOTEWORTHY</b> This study determined that the renal protective effect of Roux-en-Y gastric bypass (RYGB) in <i>db/db</i> mice was associated with elevated serum TLCA. Notably, TLCA supplementation improved renal function and alleviated podocyte inflammatory injury in <i>db/db</i> mice, which was associated with the TGR5/NF-κB pathway.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E148-E160"},"PeriodicalIF":4.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833380","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":"Celebrating 30 years of the discovery of leptin: a revolutionary shift in understanding obesity and metabolism.","authors":"Estefania P Azevedo","doi":"10.1152/ajpendo.00520.2024","DOIUrl":"10.1152/ajpendo.00520.2024","url":null,"abstract":"","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E272-E273"},"PeriodicalIF":4.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998517","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":"Macrophage immunometabolism: emerging targets for regrowth in aging muscle.","authors":"Zachary J Fennel, Ryan M O'Connell, Micah J Drummond","doi":"10.1152/ajpendo.00403.2024","DOIUrl":"10.1152/ajpendo.00403.2024","url":null,"abstract":"<p><p>The recovery from muscle atrophy is impaired with aging as characterized by improper muscle remodeling and sustained functional deficits. Age-related deficits in muscle regrowth are tightly linked with the loss of early pro-inflammatory macrophage responses and subsequent cellular dysregulation within the skeletal muscle niche. Macrophage inflammatory phenotype is regulated at the metabolic level, highlighting immunometabolism as an emerging strategy to enhance macrophage responses and restore functional muscle regrowth. Accordingly, metabolic targets with an emphasis on glycolytic, hypoxia, and redox-related pathways stand out for their role in promoting macrophage inflammation and enhancing muscle regrowth in aging. Here we highlight promising immuno-metabolic targets that could be leveraged to restore optimal pro-inflammatory macrophage function in aging and enhance muscle regrowth following muscular atrophy.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":"328 2","pages":"E186-E197"},"PeriodicalIF":4.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063098","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":"Constitutive loss of kynurenine-3-monooxygenase changes circulating kynurenine metabolites without affecting systemic energy metabolism.","authors":"Kyle D Dumont, Paulo R Jannig, Margareta Porsmyr-Palmertz, Jorge L Ruas","doi":"10.1152/ajpendo.00386.2024","DOIUrl":"10.1152/ajpendo.00386.2024","url":null,"abstract":"<p><p>Kynurenic acid (KYNA) and quinolinic acid (QUIN) are metabolites of the kynurenine pathway of tryptophan degradation with opposing biological activities in the central nervous system. In the periphery, KYNA is known to positively affect metabolic health, whereas the effects of QUIN remain less explored. Interestingly, metabolic stressors, including exercise and obesity, differentially change the balance between circulating KYNA and QUIN. Here, we hypothesized that chronically elevated levels of circulating KYNA and reduced levels of QUIN would manifest as differences in whole body energy metabolism. To test this, we used a mouse model lacking the enzyme kynurenine 3-monooxygenase (KMO), thus shunting kynurenine away from QUIN synthesis and toward KYNA production. KMO-deficient and wild-type littermate male and female mice were evaluated under chow and high-fat diets. Comprehensive kynurenine pathway metabolite profiling in plasma showed that the loss of KMO elicits robust changes in circulating levels of kynurenine metabolites. This included a 45-fold increase in kynurenine, a 26-fold increase in KYNA, and a 99% decrease in QUIN levels, depending on the diet. However, despite these changes, loss of KMO did not significantly impact whole body energy metabolism or change the transcriptomic profile of subcutaneous adipose tissue on either diet. With KMO inhibitors being considered therapeutic candidates for various disorders, this work shows that chronic systemic KMO inhibition does not have widespread metabolic effects. Our data also indicate that the beneficial effects of KYNA on metabolism may depend on its acute, intermittent elevation in circulation, akin to transient exercise-induced signals that mediate improved metabolic health.<b>NEW & NOTEWORTHY</b> The kynurenine pathway of tryptophan degradation is influenced by metabolic stressors: exercise raises circulating KYNA levels, while obesity is linked to increased QUIN. We investigated whether a mouse model lacking KMO-leading to increased circulating KYNA and decreased QUIN-would exhibit changes in energy metabolism. We found that energy metabolism was largely unaffected despite robust changes in circulating kynurenine metabolites, suggesting that systemic KMO inhibition may not have widespread metabolic effects.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E274-E285"},"PeriodicalIF":4.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977229","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 acute and chronic influence of exercise on mitochondrial dynamics in skeletal muscle.","authors":"Elya J Ritenis, Camila S Padilha, Matthew B Cooke, Christos G Stathis, Andrew Philp, Donny M Camera","doi":"10.1152/ajpendo.00311.2024","DOIUrl":"10.1152/ajpendo.00311.2024","url":null,"abstract":"<p><p>Exercise and nutritional modulation are potent stimuli for eliciting increases in mitochondrial mass and function. Collectively, these beneficial adaptations are increasingly recognized to coincide with improvements in skeletal muscle health. Mitochondrial dynamics of fission and fusion are increasingly implicated as having a central role in mediating aspects of key organelle adaptations that are seen with exercise. Exercise-induced mitochondrial adaptation dynamics that have been implicated are <i>1</i>) increases to mitochondrial turnover, resulting from elevated rates of mitochondrial synthesis (biogenesis) and degradative (mitophagy) processes and <i>2</i>) morphological changes to the three-dimensional (3-D) tubular network, known as the mitochondrial reticulum, that mitochondria form in skeletal muscle. Notably, mitochondrial fission has also been implicated in coordinating increases in mitophagy, following acute exercise. Furthermore, increased fusion following exercise training promotes increased connectivity of the mitochondrial reticulum and is associated with improved metabolism and mitochondrial function. However, the molecular basis and fashion in which exercise infers beneficial mitochondrial adaptations through mitochondrial dynamics remains to be fully elucidated. This review attempts to highlight recent developments investigating the effects of exercise on mitochondrial dynamics, while attempting to offer a perspective of the methodological refinements and potential variables, such as substrate/glycogen availability, which should be considered going forward.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E198-E209"},"PeriodicalIF":4.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492945","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 CTRP6: a biomarker and therapeutic target in metabolic diseases.","authors":"Jeevotham Senthil Kumar, Muhammad Zubair Mehboob, Xia Lei","doi":"10.1152/ajpendo.00353.2024","DOIUrl":"10.1152/ajpendo.00353.2024","url":null,"abstract":"<p><p>The rising prevalence of metabolic diseases is a significant global health concern. Beyond lifestyle management, targeting key molecules involved in metabolic regulation is essential. C1q/TNF-related protein 6 (CTRP6) is notably associated with glucose and lipid metabolism, with numerous studies highlighting its regulatory functions in metabolic diseases. This review summarizes the current knowledge on CTRP6, focusing on its gene expression profiles, protein structure, gene regulation, and role in metabolic diseases. CTRP6 is widely expressed across various tissues and features four distinct domains, with the C1q domain predicted to bind to its receptor. Notably, serum levels of CTRP6 are significantly elevated in patients with obesity and type 2 diabetes. In these conditions, adipose tissue serves as a key source of CTRP6 and its involvement in adipose tissue expansion, inflammation, and nutrient sensing has been observed in several studies. CTRP6 is also implicated in type 1 diabetes, gestational diabetes mellitus, and diabetic complications, particularly diabetic nephropathy. Although some studies have suggested that CTRP6 has protective roles in atherosclerotic cell models, myocardial infarction rat models, and ischemia/reperfusion injury mouse models, methodological issues such as unreliable antibodies and unstrict controls make it difficult to draw accurate conclusions from these studies. Patients with polycystic ovary syndrome (PCOS) exhibit elevated serum levels of CTRP6, although its direct impact on PCOS phenotypes remains unclear. In conclusion, CTRP6 emerges as a promising therapeutic target for metabolic diseases. A deeper understanding of CTRP6 will empower the scientific community to develop effective interventions to address the increasing prevalence of these diseases.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E139-E147"},"PeriodicalIF":4.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863003","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":"Method for measuring cervical vagal nerve activity in conscious rats.","authors":"Kenju Miki, Wakana Miyaura, Shizuka Ikegame, Misa Yoshimoto","doi":"10.1152/ajpendo.00184.2024","DOIUrl":"10.1152/ajpendo.00184.2024","url":null,"abstract":"<p><p>The current study aimed to propose a method to directly measure right cervical vagal nerve activity (cVNA) alongside renal sympathetic nerve activity (RSNA) in conscious rats. The right cervical vagus nerve was surgically exposed and fitted with a bipolar electrode to record cVNA. A microcatheter was used to administer levobupivacaine to selectively block afferent cVNA. Upon levobupivacaine administration, cVNA was reduced by 84%, enabling the exclusive assessment of efferent cVNA. Intravenous and intraperitoneal administration of cholecystokinin-8 (CCK-8) demonstrated that peripherally acting CCK-8 influences the central nervous system through afferent cVNA without affecting the RSNA or efferent cVNA. This technique can be highly applicable for quantifying the dynamic changes in the interaction between vagal and sympathetic nerve activities, thereby shedding light on their roles in maintaining homeostasis and developing autonomic dysfunction, as in obesity and diabetes.<b>NEW & NOTEWORTHY</b> This study proposed a method for directly measuring cervical vagal nerve activity and reversibly blocking afferent cVNA in conscious rats. It demonstrated that CCK-8, when administered intraperitoneally, distinctly influences peripheral afferent vagal nerve activity without affecting renal sympathetic nerve activity, arterial pressure, or heart rate.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E230-E241"},"PeriodicalIF":4.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942697","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":"Quantifying protein kinetics in vivo: influence of precursor dynamics on product labeling.","authors":"Huifang Yao, Seamus Kelley, Dan Zhou, Sophie VanSickle, Sheng-Ping Wang, Jennifer Piesvaux, Haihong Zhou, Hao Chen, David McKenney, David G McLaren, Jeanine E Ballard, Stephen F Previs","doi":"10.1152/ajpendo.00323.2024","DOIUrl":"10.1152/ajpendo.00323.2024","url":null,"abstract":"<p><p>Protein kinetics can be quantified by coupling stable isotope tracer methods with mass spectrometry readouts; however, interconnected decision points in the experimental design affect the complexity of the workflow and impact data interpretations. For example, choosing between a single bolus (pulse-chase) or a continuous exposure protocol influences subsequent decisions regarding when to measure and how to model the temporal labeling of a target protein. Herein, we examine the merits of in vivo tracer protocols, and we direct attention toward stable isotope tracer experiments that rely on administering a single bolus since these are generally more practical to use as compared with continuous administration protocols. We demonstrate how the interplay between precursor and product kinetics impacts downstream analytics and calculations by contrasting fast versus slow turnover precursors (e.g., ¹³C-leucine vs. ²H-water, respectively). Although the data collected here underscore certain advantages of using longer-lived precursors (e.g., ²H- or ¹⁸O-water), the results also highlight the influence of tracer recycling on measures of protein turnover. We discuss the impact of tracer recycling and consider how the sampling interval is critical for interpreting studies. Finally, we demonstrate that tracer recycling does not limit the ability to perform back-to-back studies of protein kinetics. It is possible to run experiments in which subjects are used as their own controls even though the precursor and product remain labeled following an initial tracer dosing.<b>NEW & NOTEWORTHY</b> We demonstrate a simple and robust protocol for measuring protein synthesis, the work considers problems encountered in experimental design. The logic can enable biologists with limited resources and/or can facilitate scenarios where higher throughput experiments are needed.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E173-E185"},"PeriodicalIF":4.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612364","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}