American journal of physiology. Endocrinology and metabolism最新文献

{"title":"S100A8/S100A9 impairs energy expenditure and whole body metabolism.","authors":"Anat Neumann, Irina Efimova, Inbar Shteinberg, Roni Tron, Alexander Gaskin, Noam Erez, Shani Ben-Shlomo, Nimrod Adatto Levy, Yuval Shteingard, Thomas Vogl, Johannes Roth, Yael Kuperman, Isabel Zvibel, Chen Varol, Sigal Fishman","doi":"10.1152/ajpendo.00076.2025","DOIUrl":"10.1152/ajpendo.00076.2025","url":null,"abstract":"<p><p>Thermogenic adipose tissue, specialized in dissipating chemical energy as heat, represents a promising therapeutic target for combating obesity and type 2 diabetes. S100A8/S100A9 is an inflammatory alarmin and biomarker implicated in various diseases, including obesity. Here, we investigated the role of S100A8/S100A9 in thermogenesis and whole-body energy homeostasis. Wild-type (WT) and S100A8/S100A9-deficient (<i>S100a9</i>^-/-) mice were subjected to a 14-wk high-fat diet (HFD). Thermogenic responses were assessed through cold exposure and administration of the β3-adrenergic receptor agonist CL-316,423, with additional experiments involving exogenous S100A8/S100A9 administration in WT mice. Under normal chow, <i>S100a9</i>^-/- mice exhibited a leaner phenotype compared with WT controls. Following HFD-induced obesity, <i>S100a9</i>^-/- mice displayed reduced weight gain, improved insulin sensitivity, increased lipid storage in epididymal adipose tissue, and attenuated hepatic steatosis. Physiological studies using metabolic cages revealed higher oxygen consumption and heat production in lean <i>S100a9</i>^-/- mice following chronic CL-316,423 treatment. In line, <i>S100a9</i>^-/- mice exhibited increased beiging in inguinal white adipose tissue (ingWAT), but not in brown adipose tissue (BAT), under cold exposure as well as acute and chronic CL-316,423. Conversely, exogenous S100A8/S100A9 administration under both cold challenge and chronic CL-316,423 suppressed thermogenic gene expression in ingWAT, with no significant effect in BAT. In vitro, stimulation of immortalized beige adipocytes with S100A9 led to downregulation of beige adipocyte marker genes. Collectively, these findings identify S100A8/S100A9 as a negative regulator of ingWAT beiging and energy expenditure, thereby contributing to impaired metabolic homeostasis and exacerbation of diet-induced obesity.<b>NEW & NOTEWORTHY</b> Obesity is a disorder characterized by disrupted energy homeostasis. During obesity, thermogenic pathways decline, making strategies that enhance energy expenditure a promising avenue for intervention. The alarmin complex S100A8/S100A9 is upregulated in both human and experimental models of obesity and type 2 diabetes. In this study, we identify a critical pathogenic role of S100A8/S100A9 in impairing thermogenesis in subcutaneous adipose tissue, reducing energy expenditure, and exacerbating obesity and its related complications.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E341-E354"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635887","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":"Ketone metabolites in metabolic dysfunction-associated steatotic liver disease progression: optimizing keto-therapeutic strategies.","authors":"Taylor J Kelty, Alexa A Krause, R Scott Rector","doi":"10.1152/ajpendo.00178.2025","DOIUrl":"10.1152/ajpendo.00178.2025","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) ranges from simple steatosis to hepatocellular injury, inflammation, and fibrosis, ultimately leading to end-stage liver disease. Despite its rising prevalence, treatment options remain limited, highlighting the need for novel therapeutic strategies. In recent years, ketone metabolism has emerged as a key modulator of hepatic metabolic health. Hepatic ketogenesis provides a mechanism for fatty acid mobilization. Endogenously synthesized ketone metabolites can then provide energy for hepatic nonparenchymal cells and extrahepatic tissues. Ketones also function as signaling molecules that can reduce key pathological drivers of MASLD progression. Impaired ketogenesis is observed in MASLD, contributing to metabolic inflexibility and liver dysfunction. Conversely, ketogenic interventions, including exogenous ketone supplementation and ketogenic diets, have been shown to be hepatoprotective, attenuating steatosis, inflammation, and fibrosis. Ketogenic enzyme loss- and gain-of-function studies have highlighted the roles of ketogenesis, ketolysis, and ketone metabolite conversion in MASLD, providing insights to refine keto-therapeutic strategies for disease management. This review seeks to offer a thorough examination of ketone metabolism in MASLD, exploring the mechanistic roles of ketone metabolites in disease progression, and highlighting gaps in the current literature to optimize keto-therapeutics and combat MASLD progression.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E290-E301"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582830","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":"Nonequilibrium thermodynamic analysis of human bioenergetics in obesity: implications of the second law.","authors":"Nawfal Istfan","doi":"10.1152/ajpendo.00487.2024","DOIUrl":"10.1152/ajpendo.00487.2024","url":null,"abstract":"<p><p>The fundamental principle of energy balance, a statement of the first law of thermodynamics, overlooks the second law, resulting in gaps in our knowledge of body weight regulation and obesity. This study develops research tools to implement nonequilibrium thermodynamics in human subjects based on a mitochondrial energy conversion model. A key advancement measures ATP phosphorylation through its relationship to the mitochondrial redox couple, beta-hydroxybutyrate, and acetoacetate. Applying this methodology in humans, utilizing data from a recent study, provides a comprehensive understanding of the impact of the second law. The results demonstrate that oxidative phosphorylation efficiency is approximately 57%, with minor but significant variations among individuals. Four out of 24 healthy subjects exhibited a sufficiently higher efficiency of oxidative phosphorylation and lower free energy dissipation compared to the remaining subjects. Feeding is associated with lower efficiency, a higher rate of free energy dissipation, and a slight reduction in coupling. The amount of energy utilized for useful work represents only one-third of resting energy expenditure. These findings are integrated with the current principle of energy balance to adhere to the constraints of the first and second laws. Based on theoretical modeling, it is demonstrated that interindividual differences and variations in mitochondrial efficiency and energy dissipation during specific metabolic conditions can lead to discrepancies between total energy balance and the balance of the fraction of energy used for useful work. Consequently, the constraints imposed by the second law should be incorporated into the current understanding of energy balance and obesity.<b>NEW & NOTEWORTHY</b> This article introduces the second law of thermodynamics as an integral component of the study of human energy metabolism. The concepts of efficiency and energy dissipation are unified with the current understanding of energy balance in human subjects. It is important to note that the energy utilized in biological processes constitutes only a fraction of the total energy metabolism. Measurement of this fraction relative to total energy expenditure elucidates the body's mechanisms for adapting to fuel scarcity and abundance, as exemplified by weight gain and weight loss.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E191-E209"},"PeriodicalIF":4.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309363","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":"Genealogical Rabson-Mendenhall syndrome caused by <i>INSR</i> gene mutation.","authors":"Xuewen Yuan, Ziyang Zhu, Chao Liang","doi":"10.1152/ajpendo.00285.2024","DOIUrl":"10.1152/ajpendo.00285.2024","url":null,"abstract":"<p><p>Rabson-Mendenhall syndrome (RMS) is a rare autosomal recessive disorder caused by mutations in the insulin receptor gene (<i>INSR</i>), leading to severe insulin resistance. Clinical manifestations of RMS include hypertrichosis and acanthosis nigricans. A 3-yr-old male patient presented with darkened skin on the neck, without any apparent precipitating factors, and did not exhibit symptoms of polyuria or polydipsia. Both the patient and his older sister displayed signs of hypertrichosis and acanthosis nigricans. Laboratory investigations revealed significantly elevated levels of insulin and C-peptide. Genetic testing identified two mutations in the <i>INSR</i> gene: c.3614C>T in exon 20 and c.3670G>A in exon 21, with the latter being a novel mutation previously unreported in RMS. His sister also exhibited similar clinical features and harbored the same mutations. Consequently, both siblings were diagnosed with RMS. The novel mutation c.3670G>A in exon 21, inherited from the father, is likely to impair insulin receptor function by disrupting tyrosine kinase activity, thereby contributing to the pathogenesis of genealogical RMS.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E227-E232"},"PeriodicalIF":4.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273981","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":"Corrigendum for Li et al., volume 308, 2014, p. E257-E269.","authors":"","doi":"10.1152/ajpendo.00348.2014_COR","DOIUrl":"10.1152/ajpendo.00348.2014_COR","url":null,"abstract":"","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":"329 2","pages":"E312-E313"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726521","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":"Breaking the vicious cycle: bitter compounds targeting metabolic defects and inflammation in Alzheimer's disease.","authors":"Hao Wu, Ling He, Li Dai","doi":"10.1152/ajpendo.00166.2025","DOIUrl":"10.1152/ajpendo.00166.2025","url":null,"abstract":"<p><p>Alzheimer's disease (AD), a neurodegenerative disorder characterized by progressive cognitive decline, poses an increasing global health burden among aging populations. Despite decades of research, its pathogenesis remains incompletely understood, and effective therapies are urgently needed. Growing evidence links AD progression to inflammation and type 2 diabetes mellitus (T2DM), with hyperglycemia, insulin resistance, and chronic inflammation synergistically driving neuronal dysfunction. These factors perpetuate a pathogenic \"metabolic-inflammatory cycle\": inflammatory cytokines disrupt insulin signaling, exacerbating insulin resistance, which further amplifies neuroinflammation. Whereas anti-inflammatory and antidiabetic drugs show limited clinical efficacy in AD, bitter compounds, natural and synthetic agents with pleiotropic bioactivities, offer a novel therapeutic avenue. Notably, bitter compounds such as the alkaloid berberine, the flavonoid naringenin, and synthetic bitter compounds such as denatonium benzoate and metformin exhibit dual anti-inflammatory and metabolic regulatory effects. Preclinical studies have demonstrated their ability to suppress neuroinflammation, restore insulin sensitivity, and mitigate amyloid/tau pathology, potentially disrupting the metabolic-inflammatory cycle. Emerging insights also highlight their modulation of the gut-brain axis, linking intestinal homeostasis to neuroprotection. This mini-review synthesizes current evidence on the interplay of T2DM and inflammation in AD, emphasizing how bitter compounds target immunometabolic cross talk. This review also briefly discusses the metabolic and anti-inflammatory properties of bitter compounds via the gut-brain axis, alongside their potential for combination with current anti-AD drugs, suggesting multidisciplinary collaboration. Further mechanistic studies and clinical validation are warranted to translate bitter compound-based therapies into practice, addressing unmet needs in AD management.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E266-E275"},"PeriodicalIF":4.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582831","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":"Transcriptomic analyses of peripheral blood mononuclear cells reveal age-specific basal and acute exercise responsiveness differences in humans.","authors":"Bradley A Ruple, Nicholas A Carlini, Jason S Kofoed, Helya Rostamkhani, Brady E Hanson, Isaac Wilcox, Jesse C Craig, Shelby C Osburn, Micah J Drummond, Ryan M Broxterman, Joel D Trinity","doi":"10.1152/ajpendo.00169.2025","DOIUrl":"10.1152/ajpendo.00169.2025","url":null,"abstract":"<p><p>Aging is associated with alterations in immune cell function, contributing to age-related diseases and frailty. As peripheral blood mononuclear cells (PBMCs) are key drivers of the immune response, we investigated their transcriptome using RNA-sequencing before and immediately after a single bout of high-intensity knee-extension exercise in young (young; <i>n</i> = 7, 23 ± 4 yr) and older individuals (old; <i>n</i> = 8, 65 ± 7 yr). We used bioinformatics analyses to identify the biological processes and pathways that may be altered with age and in response to acute exercise. At baseline, 665 genes differed between young and old, with notable differences in pathways involved in DNA damage/telomere stress-induced senescence, NAD signaling pathway, and oxidative stress-induced senescence. After the exercise bout, 53 genes were differentially expressed in young, whereas 1,026 genes changed in old. In young, the enriched processes and predicted pathways were linked to natural killer cells, whereas in old, these pathways were associated with cell signaling immune responses. Finally, 26 genes exhibited similar responses to exercise between groups, enriching the biological process of natural killer cell-mediated immunity regulation. Our findings indicate that PBMC gene expression and the response to acute exercise are altered with aging, where exercise induces more pronounced PBMC transcriptomic adaptations in the old. In addition, although aging is associated with increased expression of genes linked to cellular dysfunction and suppressed immune function, acute exercise attenuated these age-related differences by downregulating the genes related to those pathways. Finally, acute exercise activated similar immune-related pathways in both age groups.<b>NEW & NOTEWORTHY</b> This study demonstrates that aging alters the transcriptional landscape of PBMCs at rest and in response to acute high-intensity exercise. Older adults exhibited greater transcriptomic responsiveness to exercise, particularly in pathways related to immune signaling and cellular stress. Notably, exercise elicited shared activation of NK cell-mediated processes across age groups, suggesting a conserved immunomodulatory effect. These findings provide molecular insight into how aging and exercise interact to shape immune cell function.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E381-E390"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12352121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688647","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":"Cell-free miRNA-150-5p serves as a biomarker and regulator of PROM-related preterm labor by targeting chorionic ADAM19.","authors":"Ning Wang, Yuanyuan Liu, Kaiyi Sun, Bingying Chen, Yanyu Sui, Zhe Wang, Xiang Jiang, Li Li, Qin Li, Jingqiu Feng, Yi Tao, Lu Gao","doi":"10.1152/ajpendo.00045.2025","DOIUrl":"10.1152/ajpendo.00045.2025","url":null,"abstract":"<p><p>The prediction and treatment of spontaneous preterm labor (sPTL) are critical challenges due to obscure etiology and lack of highly specific and sensitive testing methods. Here, we extended the application of noninvasive prenatal testing into the field of sPTL prediction using high-throughput small RNA sequencing to screen the potential biomarkers for sPTL in maternal peripheral blood. We found that hsa-miR-150-5p and hsa-miR-512-3p decreased in the patients affected by sPTL, compared with either term labor or term not labor patients. The change of hsa-miR-150-5p is validated using quantitative PCR with the area under the receiver operating characteristic curve (AUROC) of hsa-miR-150-5p around 0.8272. In the discovery set, hsa-miR-150-5p exhibited an AUROC of approximately 0.8508, which was validated in an independent cohort, accurately classifying preterm samples with an AUROC of 0.8010. Moreover, we showed miR-150-5p inhibited migration and invasion of chorionic cells by directly targeting a disintegrin and metalloproteinase 19 (ADAM19). The significant increase of ADAM19 in chorion from patients affected by sPTL further indicates its inverse correlationship with miR-150-5p. ADAM19 functions as a sheddase of membrane-bound TNF-α to release the TNF-α trimer into the extracellular environment, reciprocally inducing the expression of ADAM19 to form a regenerative cycle and augmenting the migration and invasion of fetal membrane cells. Remarkably, the predictive efficiency of miR-150-5p for premature rupture of membranes (PROMs)-related sPTL sharply rose to 94.21%, indicating its potential as a biomarker for preterm premature rupture of membranes (pPROMs). These findings establish miR-150-5p both as a promising noninvasive biomarker for identifying the risk of sPTL and a key regulator in pathogenesis of pPROM.<b>NEW & NOTEWORTHY</b> MiR-150-5p is identified as a potential noninvasive biomarker associated with sPTL and regulates chorionic cell migration, invasion, and adhesion by targeting ADAM19, a member of the ADAM family, contributing to premature rupture of fetal membranes. These findings provide new insights into the molecular mechanisms of sPTL and suggest that targeting the miR-150-5p/ADAM19 axis may offer novel therapeutic strategies.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E323-E339"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635886","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":"Association of aerobic fitness and body composition with protein and major lipid class composition of high-density lipoprotein.","authors":"Emilia Ilona Lähteenmäki, Satu Lehti, Matti Jauhiainen, Anna Kankaanpää, Rabah Soliymani, Marc Baumann, Hanna Ruhanen, Reijo Käkelä, Jani Vaara, Eija Katariina Laakkonen, Katariina Öörni, Heikki Kyröläinen, Maarit Lehti","doi":"10.1152/ajpendo.00130.2025","DOIUrl":"10.1152/ajpendo.00130.2025","url":null,"abstract":"<p><p>Although high-density lipoprotein (HDL) has cardiometabolic protecting properties, interventions to raise HDL cholesterol concentration have failed to improve cardiometabolic health. Hence, HDL composition and functionality might be key factors in its anti-atherogenic capacity. Alterations in HDL composition have been linked to pathophysiological states, whereas endurance training is known to increase HDL concentration with a shift toward bigger particle sizes, but its effect on the HDL composition is not well understood. Therefore, we selected subjects with the highest and the lowest aerobic fitness from a study group resembling population and compared HDL protein and lipid composition and serum metabolic profiles using mass spectrometry, thin-layer chromatography, and nuclear magnetic resonance spectroscopy methodologies. High aerobic fitness and normal body composition were associated with elevated proportion of cholesteryl esters suggesting improved cholesterol metabolism. Low aerobic fitness and elevated amount of adipose tissue increased the proportion of phospholipids in HDL, whereas elevated proportion of triacylglycerols was associated only with higher adiposity level, suggesting modulations in particle surface fluidity and tendency for particle catabolism. Serum metabolic profiles supported the observations highlighting differences in the concentration of large HDL₂ particles, very-low-density lipoprotein, and serum triacylglycerols between the groups. Higher adipose tissue level increased proteins related to inflammation and hemostasis in HDL, whereas normal body composition was linked to increased amounts of apolipoprotein A-II and C-II suggesting improved HDL composition. Results suggest that high aerobic fitness and normal body composition have positive effects on HDL composition through reduced inflammation and better serum lipid homeostasis.<b>NEW & NOTEWORTHY</b> High aerobic fitness is linked to elevated HDL concentration and a shift toward bigger particle sizes, but its effect on the HDL composition is not well understood. For the first time, this study compared HDL lipid and proteomic compositions between two groups with differences in aerobic fitness level and body composition. The findings suggest positive modulations in HDL composition due to regular physical activity associated with better body composition, inflammation status, and serum lipid homeostasis.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E367-E380"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658144","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":"Behavior-driven monitoring of thermogenesis in mice using a thermal gradient ring.","authors":"Paulo De Melo, Nayara Pereira, Rafaela Braun Araujo, William T Festuccia, Thiago Mattar Cunha, Luiz Osório Leiria","doi":"10.1152/ajpendo.00133.2025","DOIUrl":"10.1152/ajpendo.00133.2025","url":null,"abstract":"<p><p>Accurately assessing whole body heat production requires reliable thermometry methods. In mice, common approaches include rectal temperature (RT) measurement, infrared (IR) thermography, and implanted probes. However, factors such as stress, handling, surgery, and variability limit their applicability for evaluating thermogenesis. The Thermal Gradient Ring (TGR), widely used in neuropathic pain and ion channel studies, consists of a circular structure with 12 temperature zones and an integrated camera for real-time behavior monitoring. This system allows for precise analysis of independent behavioral measures, including preferred temperature (PT), distance accumulation in the zones, locomotion pattern, and zone occupancy over time, thereby offering an indirect readout of thermoregulatory state. In this study, we evaluated TGR as a noninvasive tool to detect thermoregulatory behavior adaptations, quantifying zone occupancy time, mobility patterns across temperature gradients, and preferred temperature. Using models with both elevated (β-adrenergic stimulation and high-fat diet feeding) and reduced core body temperature [brown adipose tissue (BAT) lipectomy, uncoupling protein 1 (UCP1) deficiency, and cold exposure], we found that the TGR system reliably detects context-specific thermoregulatory behaviors that contribute to energy homeostasis, while simultaneously serving as a quantitative tool for evaluating thermogenic status. These findings suggest that TGR is a valuable tool for metabolic research, offering a reliable additional assessment for thermogenesis in mice.<b>NEW & NOTEWORTHY</b> The integration between adaptive thermogenesis and behavioral strategies governing metabolic state regulation in mice remains poorly characterized. Using a TGR system, we developed and validated a novel methodology for noninvasive, unbiased, and continuous monitoring of behavior-driven thermogenic capacity. Using loss- and gain-of-function models of BAT thermogenesis, we identified distinct behavioral strategies, mice dynamically adjusted locomotor activity and thermal zone occupancy to modulate heat production, directly reflecting their real-time monitoring of metabolic status.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E241-E253"},"PeriodicalIF":4.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526034","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}