American journal of physiology. Endocrinology and metabolism最新文献

{"title":"Roles of Circadian Clocks in Macrophage Metabolism: Implications in Inflammation, and Metabolism of Lipids, Glucose, and Amino Acids.","authors":"Mohammad Irfan Dar, Yusuf Hussain, Xiaoyue Pan","doi":"10.1152/ajpendo.00009.2025","DOIUrl":"https://doi.org/10.1152/ajpendo.00009.2025","url":null,"abstract":"<p><p>Macrophages are essential immune cells that play crucial roles in inflammation and tissue homeostasis, and are important regulators of metabolic processes, such as the metabolism of glucose, lipids, and amino acids. The regulation of macrophage metabolism by circadian clock genes has been emphasized in many studies. Changes in metabolic profiles occurring after the perturbation of macrophage circadian cycles may underlie the etiology of several diseases. Specifically, chronic inflammatory disorders, such as atherosclerosis, diabetes, cardiovascular diseases, and liver dysfunction, are associated with poor macrophage metabolism. Developing treatment approaches that target metabolic and immunological ailments requires an understanding of the complex relationships among clock genes, disease etiology, and macrophage metabolism. This review explores the molecular mechanisms through which clock genes regulate lipid, amino acid, and glucose metabolism in macrophages, and discusses their potential roles in the development and progression of metabolic disorders. The findings underscore the importance of maintaining circadian homeostasis in macrophage function as a promising avenue for therapeutic intervention in diseases involving metabolic dysregulation, given its key roles in inflammation and tissue homeostasis. Moreover, reviewing the therapeutic implications of circadian rhythm in macrophages can help minimize the side effects of treatment. Novel strategies may be beneficial in treating immune-related diseases cause by shifted and blunted circadian rhythms via light exposure, jet lag, seasonal changes, and shift work or disruption to the internal clock (such as stress or disease).</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794537","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":"Central lipid sensing pathways contribute to the control of puberty and its alterations in conditions of obesity.","authors":"Elvira Rodríguez-Vázquez, Álvaro Aranda-Torrecillas, María López-Sancho, Manuel Jiménez-Puyer, Silvia Daza-Dueñas, Alexia Barroso, Verónica Sobrino, Francisco Gaytan, Elia Obis, Juan M Castellano, Manuel Tena-Sempere","doi":"10.1152/ajpendo.00493.2024","DOIUrl":"https://doi.org/10.1152/ajpendo.00493.2024","url":null,"abstract":"<p><p>Childhood obesity, especially in girls, often correlates with advanced puberty and long-term comorbidities. Among the central circuits controlling energy homeostasis, hypothalamic lipid sensing pathways, involving free fatty-acid receptors (FFARs), peroxisome proliferator-activated receptors (PPAR) and the bile-acid (BA) receptor, TGR5, have been recognized as major players, with putative pathogenic roles in obesity and its complications. However, their contribution to pubertal regulation and obesity-induced pubertal alterations remains largely unexplored. We describe herein changes in the hypothalamic profiles of specific lipid species, including certain fatty-acyls, BA derivatives and several glycerol(phospho)lipids, during the juvenile-pubertal transition and conditions of overweight linked to precocious puberty in female rats. Hypothalamic expression of the FFAR, <i>Gpr84</i>, as well as <i>Ppar-γ</i> and <i>Tgr5</i> gradually increased during infantile-prepubertal transition, while early-overfeeding increased hypothalamic mRNA levels of the FFARs, <i>Gpr43</i> and <i>Gpr84</i>. Expression of <i>Gpr84</i>, <i>Ppar-α</i> and <i>Tgr5</i> was documented in FACS-isolated Kiss1 neurons from juvenile and pubertal female mice. Central pharmacological gain- and loss-of-function manipulations of Gpr84-, PPAR- or TGR5-signaling in prepubertal lean and early-overfed female rats resulted in specific changes in pubertal timing. In lean rats, central blockade of PPAR-γ/α delayed puberty onset, while in early-overfed rats, central stimulation of TGR5 signaling partially prevented obesity-induced advanced puberty; effects marginally observed also after Gpr84 inhibition. Our results disclose the role of brain lipid-sensing pathways in the control of puberty, with a variable contribution of central FFAR-, PPAR- and TGR5-signaling depending on the maturational and nutritional status.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762684","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":"Effect of in utero metformin exposure in gestational diabetes mellitus on infant mesenchymal stem cell metabolism.","authors":"Ericka M Biagioni, John C Rowe, Sripallavi Yendamuri, Breanna L Wisseman, Donghai Zheng, Guofang Zhang, Deborah M Muoio, James E DeVente, Kelsey H Fisher-Wellman, P Darrell Neufer, Linda E May, Nicholas T Broskey","doi":"10.1152/ajpendo.00428.2024","DOIUrl":"10.1152/ajpendo.00428.2024","url":null,"abstract":"<p><p>Offspring exposed to metformin treatment for gestational diabetes mellitus (GDM) experience altered growth patterns that increase the risk for developing cardiometabolic diseases later in life. The adaptive cellular mechanisms underlying these patterns remain unclear. Therefore, the objective of this study was to determine whether chronic in utero metformin exposure associated with GDM treatment elicits infant cellular metabolic adaptations. In a cross-sectional design, 22 pregnant women diagnosed with GDM and treated exclusively with metformin (Met; <i>n</i> = 12) or diet (A1DM; <i>n</i> = 10) were compared. Umbilical cord-derived mesenchymal stem cells (MSCs) were used as a model to study infant metabolism in vitro. OXPHOS and citrate synthase content were assessed by Western blot and intracellular lipid content was measured by Oil Red-O staining. Substrate oxidation and insulin action were measured with ¹⁴C radiolabeled glucose and oleate at baseline and following a 24-h lipid challenge. Mitochondrial respiration was assessed by high-resolution respirometry. Although no differences in infant birth measures were observed between groups, MSC outcomes revealed lower oleate oxidation rates (<i>P</i> = 0.03) and lower mitochondrial capacity (<i>P</i> = 0.009) among Met-MSCs. These findings suggest differences in energy metabolism may be present at birth among offspring exposed to metformin in utero. Lower oleate oxidation and mitochondrial capacity in infant MSC may contribute to altered growth patterns that have been reported among offspring of metformin-treated pregnant women with GDM.<b>NEW & NOTEWORTHY</b> Mesenchymal stem cells (MSCs) of infants born to women with gestational diabetes mellitus (GDM) treated by metformin display lower rates of oleate oxidation despite no limitations in lipid availability compared with GDM treated by diet. Mitochondrial capacity was also lower among infant MSCs from metformin-treated GDM.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E567-E578"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613025","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":"Discovery of a novel regulator, 3β-sulfate-5-cholestenoic acid, of lipid metabolism and inflammation.","authors":"Yaping Wang, Arun J Sanyal, Phillip Hylemon, Shunlin Ren","doi":"10.1152/ajpendo.00426.2024","DOIUrl":"10.1152/ajpendo.00426.2024","url":null,"abstract":"<p><p>Mitochondrial oxysterols, cholestenoic acid (CA), 25-hydroxycholesterol (25HC), and 27-hydroxycholesterol (27HC), are potent regulators involved in many important biological events. This study aimed to investigate the metabolic pathways of these oxysterols and their roles between hepatocytes and macrophages. LC-MS/MS analysis showed a novel regulatory molecule, 3β-sulfate-5-cholestenoic acid (3SCA), following the addition of CA in media culturing hepatocytes. Further study showed that 3SCA could also be derived from 27HC. In comparison, 25HC was converted to 25HC3S, which mostly remained in the cells and nuclei. The functional study showed that 3SCA significantly downregulated the expression of genes involved in lipid metabolism in hepatocytes and suppressed gene expression of proinflammatory cytokines induced by lipopolysaccharide in human macrophages. Based on the results, we conclude that 3SCA acts as a secretory regulator for the regulation of lipid metabolism and inflammatory responses in hepatocytes and macrophages. These findings shed light on understanding the unique metabolic pathways of these oxysterols and their possible roles in liver tissues.<b>NEW & NOTEWORTHY</b> This study identifies a novel oxysterol metabolite, 3β-sulfate-5-cholestenoic acid (3SCA), secreted by hepatocytes, which regulates lipid metabolism and inflammatory responses in hepatocytes and macrophages. These findings reveal previously unknown metabolic pathways of mitochondrial oxysterols and their roles in the progression and recovery of metabolic dysfunction-associated steatotic liver disease (MASLD), offering novel insights into potential therapeutic targets.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E543-E554"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565780","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 effect of a leptin phenotype on weight change and energy expenditure responses to acute and prolonged energetic stressors.","authors":"Kaja Falkenhain, Tomás Cabeza De Baca, Emma J Stinson, Eric Ravussin, Paolo Piaggi, Jonathan Krakoff, Leanne M Redman","doi":"10.1152/ajpendo.00067.2025","DOIUrl":"10.1152/ajpendo.00067.2025","url":null,"abstract":"<p><p>Leptin is a hormone produced by adipocytes that plays a crucial role in regulating energy homeostasis and body mass. Despite its close correlation with body fat, up to ∼40% of variation in plasma leptin concentration remains unexplained, allowing for the classification of a distinct \"leptin phenotype.\" This leptin phenotype-characterized by either relatively high or relatively low leptin concentration relative to an individual's level of body fat-presents an intriguing opportunity to test whether relatively higher (compared with lower) leptin concentrations differentially affect energy expenditure, metabolic adaptation, and susceptibility to weight change in response to energy balance perturbations. To test this hypothesis, we characterized the energy expenditure and weight change response between the two leptin phenotypes (relatively high vs. low) using three distinct experimental contexts: a cross-sectional analysis (<i>n</i> = 104), acute (24-h) perturbations with fasting and overfeeding (<i>n</i> = 77), and chronic perturbations with 24-mo caloric restriction (<i>n</i> = 144) or 8-wk overfeeding (<i>n</i> = 28). Leptin phenotype did not explain variations in energy expenditure responses either in cross-sectional analyses or in response to acute or prolonged energetic stressors. Moreover, leptin phenotype was not a determinant of weight change in response to energy restriction or surplus, or subsequent weight recovery. These results suggest that classifying individuals based on a leptin phenotype does not allow to detect differential susceptibility to energy expenditure adaptations or weight change.<b>NEW & NOTEWORTHY</b> Leptin is linked to body fat, but unexplained variation remains. This study challenges the idea that distinct leptin phenotypes-characterized by relatively high or low leptin concentration for a given level of body fat-affects energy expenditure or weight change in response to acute or prolonged energy stressors. We found no association between leptin phenotypes and energy expenditure or weight change either cross-sectionally or in response to acute or prolonged over- or underfeeding.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E579-E587"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646957","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":"Prolonged postweaning protein restriction induces gut dysbiosis and colonic dysfunction in male mice.","authors":"Kênia Moreno de Oliveira, Gabriela Moreira Soares, Joel Alves da Silva Junior, Bruna Lourençoni Alves, Israelle Netto Freitas, Kelly Cristina Pereira Bem, Felippe Mousovich-Neto, Rosane Aparecida Ribeiro, Everardo Magalhães Carneiro","doi":"10.1152/ajpendo.00229.2024","DOIUrl":"10.1152/ajpendo.00229.2024","url":null,"abstract":"<p><p>Insufficient or imbalanced protein can disrupt gut microbiota, potentially compromising gut barrier function and increasing health risks. Herein, we investigated the effects of protein restriction on cecal microbiota and colon morphofunction in male mice. From 30 to 120 days of age, <i>C57Bl/6</i> mice were fed a control protein diet [14% protein, control (C) group] or a low-protein diet [6% protein, protein-restricted (R) group]. At the end of the experimental period, R mice exhibited typical features of undernutrition, such as reduced body weight, hypoalbuminemia, and hypoproteinemia. In addition, despite the hyperphagia displayed in the R group, these mice presented a decreased amount of excreted feces and less energy content in feces. Cecal microbiota analysis demonstrated that protein restriction led to reductions in Shannon and Simpson indices and, therefore, dysbiosis. This effect was accompanied by morphological modifications in the proximal colon of R mice, such as <i>1</i>) reduction in the total area of neurons of myenteric plexus; <i>2</i>) increased number of goblet cells, with mucin droplets less developed; <i>3</i>) reductions in crypt depth and diameter; <i>4</i>) decreases in gene expressions for mucins and in the tight junction proteins expression; <i>5</i>) enhanced paracellular permeability and expression of pro-inflammatory cytokines (tumor necrosis factor α, toll-like receptor 4, interferon γ, interleukin 1β, and interleukin 6), decreased anti-inflammatory cytokines (interleukins 4 and 10) in the colon, and increased plasma LPS binding protein concentrations. Therefore, protein restriction induced gut dysbiosis and may result in structural and functional negative impacts on the proximal colon barrier against luminal bacteria.<b>NEW & NOTEWORTHY</b> Prolonged postweaning protein restriction induced gut dysbiosis and led to a reduced neuron area in the myenteric plexus, with increased but underdeveloped goblet cells. Protein restriction decreased colonic crypt depth and diameter, and increased paracellular permeability due to lower expression of mucin-related genes and tight junction proteins. The diminished barrier function resulted in systemic inflammation, evidenced by elevated plasma LPS-binding protein and pro-inflammatory markers in the colon.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E599-E610"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522443","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":"Hypothalamus and brainstem circuits in the regulation of glucose homeostasis.","authors":"Zitian Lin, Yunxin Xuan, Yingshi Zhang, Qirui Zhou, Weiwei Qiu","doi":"10.1152/ajpendo.00474.2024","DOIUrl":"10.1152/ajpendo.00474.2024","url":null,"abstract":"<p><p>The central nervous system (CNS) senses and integrates blood glucose status, regulating its levels through communication with peripheral organs. Since traditional wisdom holds that the hypothalamus primarily controls glucose homeostasis, the brainstem, although less studied, has been emerging as a key player in blood glucose metabolism. Although the brainstem is reciprocally wired with the hypothalamus, their interactions are crucial for glucose control. Here, we focus on classic discoveries and recent advancements of hypothalamic and brainstem nodes that regulate glucose homeostasis. Based on the current progress and development for central regulation of blood sugar, we propose that the circuitry and cellular mechanisms for how hypothalamus and brainstem coordinate in blood sugar regulation are crucial; hence, a deeper understanding of both nuclei could shed light on a future cure for diabetes.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E588-E598"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565781","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":"Six-hour hypoxia-induced protein degradation in M. gastrocnemius of 24-day-old mice by activating FOXO1 and suppressing AKT-mTORC1.","authors":"Jingyi Song, Marcel Jaklofsky, Claudia Carmone, Vincent de Boer, Niels Wever, Jaap Keijer, Sander Grefte","doi":"10.1152/ajpendo.00508.2024","DOIUrl":"10.1152/ajpendo.00508.2024","url":null,"abstract":"<p><p>Long-term hypoxia has been associated with skeletal muscle atrophy, including increased protein degradation over protein synthesis. This contrasts sharply with muscle hypertrophy and net protein synthesis occurring in the developing skeletal muscle of young mice. Here, we aimed to understand the impact of acute, physiologically plausible environmental hypoxia on muscle proteostasis of the M. gastrocnemius of young mice. Fasted prepubertal, 24-day-old male B6JRccHsd(B6J)-<i>Nnt⁺</i>/Wuhap mice with similar body weight and lean mass were exposed to normobaric hypoxia (12% O₂) or normoxia (20.9% O₂) for 6 h. The transcriptome (<i>n</i> = 12) and protein (<i>n</i> = 6) responses of the M. gastrocnemius were analyzed. A hypoxic response of M. gastrocnemius was confirmed by increased expression of hypoxia-inducible factor 1 (HIF1) (<i>Ankrd37</i> and <i>Ddit4</i>) and forkhead box-O (FOXO) 1 (<i>Depp1</i> and <i>Ddit4</i>) target genes. RNA-Seq analysis revealed that hypoxia activated FOXO signaling, which was confirmed by increased FOXO1 protein levels and decreased p-AKT/AKT ratio. Detailed mapping of the FOXO1 pathway suggests a strong FOXO1-mediated hypoxic effect on protein degradation and synthesis. A central role of <i>Atf4</i> is suggested by the hypoxic-dependent positive correlations with FOXO1, FBXO32, <i>Depp1</i>, <i>Eif4ebp1</i>, and <i>Ddit4</i>. Further analyses showed increased FBXO32, which positively correlated with FOXO1, and decreased p-S6K/S6K and p-4E-BP1/4E-BP1 ratios. Our results showed for the first time that a 6-h exposure to 12% O₂ normobaric hypoxia in 24-day-old mice activates FOXO1 signaling in M. gastrocnemius, resulting in decreased protein synthesis and increased protein degradation most likely via reduced energy availability, which may be relevant for infant air or high altitude traveling.<b>NEW & NOTEWORTHY</b> We newly investigated an acute (6 h) hypoxic exposure (12% O₂) in developing and growing M. gastrocnemius of 24-day-old mice. This acute hypoxia significantly enhanced muscle protein breakdown via the activation of FOXO1 and subsequently FBXO32, whereas also suppressing protein synthesis via the reduced p-S6K/S6K and p-4E-BP1/4E-BP1 and thus AKT-mTORC1 pathway. Together these changes observed could potentially hamper the muscle development of young mice.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E620-E632"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646953","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":"Vertical sleeve gastrectomy and semaglutide have distinct effects on skeletal health and heart function in obese male mice.","authors":"Caroline de Carvalho Picoli, Sergey Tsibulnikov, Mavy Ho, Victoria DeMambro, Tiange Feng, May Eltahir, Phuong T Le, Carolyn Chlebek, Clifford J Rosen, Sergey Ryzhov, Ziru Li","doi":"10.1152/ajpendo.00521.2024","DOIUrl":"10.1152/ajpendo.00521.2024","url":null,"abstract":"<p><p>Obesity is a global health challenge associated with significant metabolic and cardiovascular risks. Bariatric surgery and glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are effective interventions for weight loss and metabolic improvement, yet their comparative effects on systemic metabolism-particularly energy metabolism, bone health, and heart function-remain unclear. In this study, obese male mice underwent vertical sleeve gastrectomy (VSG), 6 wk of GLP-1RA (semaglutide) treatment, or sham procedure with saline injection as controls. Dynamic changes in body weight, food intake, fat mass, lean mass, and bone mineral density were monitored. Energy metabolism was assessed using indirect calorimetry. Bone parameters and heart function were evaluated by microcomputed tomography or echocardiography, respectively. Compared with obese controls, VSG and semaglutide treatment comparably reduced body weight and improved glucose metabolism. However, VSG decreased energy expenditure, whereas both treatments similarly promoted lipid utilization. Semaglutide treatment increased ambulatory activity during nighttime. VSG led to significant bone loss, although 6 wk of semaglutide treatment had no significant effects on the skeleton. Cardiovascular outcomes also differed: VSG increased stroke volume without altering heart mass, whereas semaglutide reduced heart mass and transiently elevated heart rate. These findings underscore the importance of carefully weighing the benefits and potential risks of different weight loss treatments when addressing obesity and its systemic complications.<b>NEW & NOTEWORTHY</b> Comparative studies of surgical and pharmaceutical approaches to weight loss offer critical insights that can guide clinical decision-making for managing obesity. VSG and semaglutide exhibit comparable efficacy in promoting weight reduction and improving glucose metabolism. VSG reduces energy expenditure, whereas semaglutide increases animal activity during nighttime. VSG leads to significant bone loss, whereas semaglutide preserves bone mass independent of weight loss. VSG improves cardiac outcomes, whereas semaglutide transiently affects heart function.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E555-E566"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613027","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":"Central FGF19 signaling enhances energy homeostasis and adipose tissue thermogenesis through sympathetic activation in obese mice.","authors":"Lucas Zangerolamo, Marina Carvalho, Carina Solon, Davi Sidarta-Oliveira, Gabriela M Soares, Carine Marmentini, Antonio C Boschero, Yu-Hua Tseng, Licio A Velloso, Helena C L Barbosa","doi":"10.1152/ajpendo.00488.2024","DOIUrl":"10.1152/ajpendo.00488.2024","url":null,"abstract":"<p><p>Fibroblast growth factor 19 (FGF19) signaling in the brain is associated with body weight loss, reduced food intake, and improved glycemic control in obese mice through unclear mechanisms. Here, we investigated the effects of central FGF19 administration on peripheral tissues, focusing on adipose tissue and its contributions to body weight loss. Using single-cell RNA sequencing of the adult murine hypothalamus, we found that FGF19 has the potential to target multiple cell populations, including astrocytes-tanycytes, microglia, neurons, and oligodendrocytes. Central delivery of FGF19 decreased body weight gain and ameliorated glucose-insulin homeostasis in diet-induced obese (DIO) mice. These results were accompanied by increased energy expenditure and reduced peripheric inflammation. Notably, these effects were attributable to the increased activity of thermogenic adipocytes, as upregulated thermogenic markers in brown and inguinal adipose tissue and improved cold tolerance were induced by central FGF19. However, under blunted sympathetic activity, the described effects were abolished. Moreover, cold exposure induced upregulation of FGF19 receptors and coreceptors specifically in the hypothalamus, suggesting a critical metabolic adaptation for thermoregulation and energy homeostasis. Our findings indicate that central FGF19 signaling improves energy homeostasis in DIO mice, at least in part, by stimulating sympathetic activity and adipose tissue thermogenesis. These findings highlight FGF19's potential as a therapeutic target for obesity and metabolic disorders.<b>NEW & NOTEWORTHY</b> Although most studies associate central fibroblast growth factor 19 (FGF19) with reduced food intake, our findings highlight its role in enhancing thermogenesis in white and brown adipose tissues through sympathetic activation. Central FGF19 not only regulates feeding but also drives peripheral adaptations critical for energy homeostasis and body weight control under obesogenic conditions. These insights underscore the significance of top-down mechanisms in FGF19 action and its therapeutic potential for combating obesity.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E524-E542"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584348","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}