American journal of physiology. Endocrinology and metabolism最新文献

{"title":"Duration of Morning Hyperinsulinemia Determines Hepatic Glucose Uptake and Glycogen Storage Later in the Day","authors":"Hannah L. Waterman, Mary Courtney Moore, Marta S. Smith, Ben Farmer, Melanie Scott, Dale S. Edgerton, Alan D. Cherrington","doi":"10.1152/ajpendo.00170.2024","DOIUrl":"https://doi.org/10.1152/ajpendo.00170.2024","url":null,"abstract":"American Journal of Physiology-Endocrinology and Metabolism, Ahead of Print. <br/>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142183601","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":"Interaction of MMP-9 in the active phase of Graves' disease with and without ophthalmopathy","authors":"Cinthia Minatel Riguetto, Eduardo Buzolin Barbosa, Camila Cristina Atihe, Fabiano Reis, Monica Alves, Denise Engelbrecht Zantut-Wittmann","doi":"10.1152/ajpendo.00166.2024","DOIUrl":"https://doi.org/10.1152/ajpendo.00166.2024","url":null,"abstract":"American Journal of Physiology-Endocrinology and Metabolism, Ahead of Print. <br/>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142183603","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":"Effects of 1,144 km of road cycling performed in 7 days: a cardiometabolic imaging study.","authors":"Dominic J Chartrand, Adrien Murphy-Després, Isabelle Lemieux, Eric Larose, Paul Poirier, Jean-Pierre Després, Natalie Alméras","doi":"10.1152/ajpendo.00098.2024","DOIUrl":"10.1152/ajpendo.00098.2024","url":null,"abstract":"<p><p>This cardiometabolic imaging study was designed to document the adaptation of middle-aged recreational cyclists to a large exercise prescription not aiming at weight loss. Eleven middle-aged recreational male cyclists traveled 1,144 km over seven consecutive days. A comprehensive cardiometabolic profile including visceral and ectopic adiposity assessed by magnetic resonance imaging was obtained at baseline and following the exercise week. Cardiorespiratory fitness (CRF) was measured using maximal cardiopulmonary exercise testing. During the week, heart rate was monitored to calculate individual energy expenditure. Baseline characteristics of cyclists were compared with 86 healthy males in the same age range. Cyclists presented higher baseline CRF (+9.2 mL/kg/min, <i>P</i> < 0.0001) and lower subcutaneous (-56.2 mL, <i>P</i> < 0.05) and liver (-3.3%, <i>P</i> < 0.05) fat compared with the reference group. Despite the large energy expenditure during the cycling week, the increase in energy intake limited decreases in body weight (-0.8 ± 0.9 kg, <i>P</i> < 0.05) and body mass index (-0.3 ± 0.3 kg/m², <i>P</i> < 0.05). Loss of fat mass (-1.5 ± 1.0 kg, <i>P</i> < 0.001) and a trend toward an increased lean mass (+0.8 ± 1.2 kg, <i>P</i> < 0.07) were observed. Visceral adiposity (-14.1 ± 14.2 mL, <i>P</i> < 0.01) and waist circumference (-3.2 ± 1.7 cm, <i>P</i> < 0.0001) decreased, whereas subcutaneous (-2.7 ± 5.1 mL, NS), liver (-0.5 ± 0.9%, NS), and cardiac (-0.3 ± 2.3 mL, NS) fat remained unchanged. This cardiometabolic imaging study documents middle-aged recreational cyclists' subcutaneous and visceral adiposity as well as cardiac and liver fat responses to a large volume of endurance exercise despite an increase in energy intake aimed at limiting weight loss.<b>NEW & NOTEWORTHY</b> Even when being accompanied by a substantial increase in energy intake to compensate energy expenditure and limit weight loss, a large volume of endurance exercise performed within a short period of time is associated with a significant reduction in visceral adiposity. High cardiorespiratory fitness is associated with low levels of liver fat in middle-aged males.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750915","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":"Intermittent fasting and high-intensity interval training do not alter gut microbiota composition in adult women with obesity.","authors":"Gabriela Batitucci, Otávio G Almeida, Elaine C P De Martinis, Isabela Solar, Dennys E Cintra, Ellen Cristini de Freitas","doi":"10.1152/ajpendo.00310.2023","DOIUrl":"10.1152/ajpendo.00310.2023","url":null,"abstract":"<p><p>Obesity is advancing at an accelerated pace, and yet its treatment is still an emerging field. Although studies have demonstrated the role of the microbiota in the pathogenesis of obesity, this is the first study to show the effects of intermittent fasting (IF), combined or not with exercise, and high-intensity interval training (HIIT) on the gut microbiota composition in women with obesity. Our hypothesis is that IF combined with HIIT can promote the remodeling of the composition and function of the gut microbiota. Thirty-six women with obesity, aged between 18 and 40 yr, participated in the study. They were randomly divided into three groups: <i>1</i>) IF associated with HIIT group [IF + exercise group (EX), <i>n</i> = 15]; <i>2</i>) HIIT group (EX, <i>n</i> = 11); and <i>3</i>) IF group (IF, <i>n</i> = 10). Interventions took place over 8 wk, and all assessments were performed preintervention and postintervention. The HIIT circuit was performed 3 times/wk, for 25 min/session. The IF protocol was a 5:2 (2 times/wk). Multiplex analysis of inflammatory cytokines, sequencing of the <i>16S rRNA</i> gene, and gas chromatography to measure fecal concentrations of short-chain fatty acids (SCFAs) were performed. This study was registered on ClinicalTrials.gov (NCT05237154). Exercise increased fecal acetate concentrations (<i>P</i> = 0.04), but no changes were observed in the composition and functional profile of the microbiota. The interventions did not change the composition of the microbiota, but exercise may play a modulatory role in the production of acetate. This investigation provides clinical insights into the use of IF and HIIT for women with obesity.<b>NEW & NOTEWORTHY</b> This is the first investigation about alternate-day fasting combined with HITT on the gut microbiota of obese women. The study contributes to the advancement of human science involving IF and HIIT, popular strategies for managing obesity. Previous evidence has explored IF in modulating the microbiota in animal models or specific populations and clinical conditions. Despite the subtle outcomes, this study has relevance and originality in the field of gut microbiota knowledge.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise training and spexin ameliorate thyroid changes in obese type 2 diabetic rats: the possible interlaying mechanisms.","authors":"Fatma H Rizk, Ramez A E Barhoma, Mervat H El-Saka, Hoda A Ibrahim, Rehab M El-Gohary, Radwa Ismail, Shaimaa M Motawea, Ola Salem, Islam Ibrahim Hegab","doi":"10.1152/ajpendo.00213.2024","DOIUrl":"10.1152/ajpendo.00213.2024","url":null,"abstract":"<p><p>Thyroid dysfunction and diabetes mellitus are prevalent endocrine disorders that often coexist and influence each other. The role of spexin (SPX) in diabetes and obesity is well documented, but its connection to thyroid function is less understood. This study investigates the influence of exercise (EX) and SPX on thyroid hypofunction in obese type 2 diabetic rats. Rats were divided into normal control, obese diabetic sedentary, obese diabetic EX, and obese diabetic SPX groups, with subdivisions for M871 and HT-2157 treatment in the latter two groups. High-fat diet together with streptozotocin (STZ) injection induced obesity and diabetes. The EX group underwent swimming, and the SPX group received SPX injections for 8 wk. Results showed significant improvements in thyroid function and metabolic, oxidative, and inflammatory states with EX and SPX treatment. The study also explored the involvement of galanin receptor isoforms (GALR)2/3 in SPX effects on thyroid function. Blocking GALR2/3 receptors partially attenuated the beneficial effects, indicating their interaction. These findings underscore the importance of EX and SPX in modulating thyroid function in obesity and diabetes. Comprehending this interplay could enable the development of new treatment approaches for thyroid disorders associated with obese type 2 diabetes. Additional research is necessary to clarify the exact mechanisms connecting SPX, EX activity, and thyroid function.<b>NEW & NOTEWORTHY</b> This study proves, for the first time, the beneficial effects of SPX on thyroid dysfunction in obese diabetic rats and suggests that SPX mediates the EX effect on thyroid gland and exerts its effect mainly via GALR2.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625684","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":"Circulating exosomal circRNA-miRNA-mRNA network in a familial partial lipodystrophy type 3 family with a novel <i>PPARG</i> frameshift mutation c.418dup.","authors":"Liyuan Zhou, Shunhua Li, Jing Ren, Dongmei Wang, Ruiqi Yu, Yuxing Zhao, Qian Zhang, Xinhua Xiao","doi":"10.1152/ajpendo.00094.2024","DOIUrl":"10.1152/ajpendo.00094.2024","url":null,"abstract":"<p><p>Familial partial lipodystrophy 3 (FPLD3) is a rare genetic disorder caused by loss-of-function mutations in the <i>PPARG</i> gene, characterized by a selective absence of subcutaneous fat and associated metabolic complications. However, the molecular mechanisms of FPLD3 remain unclear. In this study, we recruited a 17-yr-old Chinese female with FPLD3 and her family, identifying a novel <i>PPARG</i> frameshift mutation (exon 4: c.418dup: p.R140Kfs*7) that truncates the PPARγ protein at the seventh amino acid, significantly expanding the genetic landscape of FPLD3. By performing next-generation sequencing of circular RNAs (circRNAs), microRNAs (miRNAs), and mRNAs in plasma exosomes, we discovered 59 circRNAs, 57 miRNAs, and 299 mRNAs were significantly altered in the mutation carriers compared with the healthy controls. Integration analysis highlighted that the circ_0001597-miR-671-5p pair and 18 mRNAs might be incorporated into the metabolic regulatory networks of the FPLD3 induced by the novel <i>PPARG</i> mutation. Functional annotation suggested that these genes were significantly enriched in glucose- and lipid metabolism-related pathways. Among the circRNA-miRNA-mRNA network, we identified two critical regulators, early growth response-1 (<i>EGR1</i>), a key transcription factor known for its role in insulin signaling pathways and lipid metabolism, and 1-acylglycerol-3-phosphate <i>O</i>-acyltransferase 3 (<i>AGPAT3</i>), which gets involved in the biosynthesis of triglycerides and lipolysis. Circ_0001597 regulates the expression of these genes through miR-671-5p, potentially contributing to the pathophysiology of FPLD3. Overall, this study clarified a circulating exosomal circRNA-miRNA-mRNA network in a FPLD3 family with a novel <i>PPARG</i> mutation, providing evidence for exploring promising biomarkers and developing novel therapeutic strategies for this rare genetic disorder.<b>NEW & NOTEWORTHY</b> Through the establishment of a ceRNA regulatory networks in a novel <i>PPARG</i> frameshift mutation c.418dup-induced FPLD3 pedigree, this study reveals that circ_0001597 may contribute to the pathophysiology of FPLD3 by sequestering miR-671-5p to regulate the expression of <i>EGR1</i> and <i>AGPAT3</i>, pivotal genes situated in the triglyceride (TG) synthesis and lipolysis pathways. Current findings expand our molecular understanding of adipose tissue dysfunction, providing potential blood biomarkers and therapeutic avenues for lipodystrophy and associated metabolic complications.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625683","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 ghrelin on glucose tolerance, gut hormones, appetite, and food intake after sleeve gastrectomy.","authors":"Nora Hedbäck, Marie-Louise Dichman, Morten Hindsø, Carsten Dirksen, Nils Brun Jørgensen, Kirstine Nyvold Bojsen-Møller, Viggo B Kristiansen, Jens F Rehfeld, Bolette Hartmann, Jens Juul Holst, Maria Saur Svane, Sten Madsbad","doi":"10.1152/ajpendo.00177.2024","DOIUrl":"10.1152/ajpendo.00177.2024","url":null,"abstract":"<p><p>Ghrelin is an appetite-stimulating hormone secreted from the gastric mucosa in the fasting state, and secretion decreases in response to food intake. After sleeve gastrectomy (SG), plasma concentrations of ghrelin decrease markedly. Whether this affects appetite and glucose tolerance postoperatively is unknown. We investigated the effects of ghrelin infusion on appetite and glucose tolerance in individuals with obesity before and 3 mo after SG. Twelve participants scheduled for SG were included. Before and 3 mo after surgery, a mixed-meal test followed by an ad libitum meal test was performed with concomitant infusions of acyl-ghrelin (1 pmol/kg/min) or placebo. Infusions began 60 min before meal intake to reach a steady state before the mixed-meal and were continued throughout the study day. Two additional experimental days with 0.25 pmol/kg/min and 10 pmol/kg/min of acyl-ghrelin infusions were conducted 3 mo after surgery. Both before and after SG, postprandial glucose concentrations increased dose dependently during ghrelin infusions compared with placebo. Ghrelin infusions inhibited basal and postprandial insulin secretion rates, resulting in lowered measures of β-cell function, but no effect on insulin sensitivity was seen. Ad libitum meal intake was unaffected by the administration of ghrelin. In conclusion, ghrelin infusion increases postprandial plasma glucose concentrations and impairs β-cell function before and after SG but has no effect on ad libitum meal intake. We speculate that the lower concentration of ghrelin after SG may impact glucose metabolism following this procedure.<b>NEW & NOTEWORTHY</b> Ghrelin's effect on glucose tolerance and food intake following sleeve gastrectomy (SG) was evaluated. Acyl-ghrelin was infused during a mixed-meal and ad libitum meals before and 3 mo after surgery. Postprandial glucose concentrations increased during ghrelin infusions, both before and after surgery, while insulin production was inhibited. However, ad libitum meal intake did not differ during ghrelin administration compared with placebo. The decreased ghrelin concentration following SG may contribute to the glycemic control after surgery.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854496","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":"Maternal genetics and diet modulate vitamin A homeostasis of the offspring and affect the susceptibility to obesity in adulthood in mice.","authors":"Ramkumar Srinivasagan, Sebastià Galmés, Denitsa Vasileva, Paula Rubí, Andreu Palou, Jaume Amengual, Joan Ribot, Johannes von Lintig, M Luisa Bonet","doi":"10.1152/ajpendo.00116.2024","DOIUrl":"10.1152/ajpendo.00116.2024","url":null,"abstract":"<p><p>Perinatal nutrition exerts a profound influence on adult metabolic health. This study aimed to investigate whether increased maternal vitamin A (VA) supply can lead to beneficial metabolic phenotypes in the offspring. The researchers utilized mice deficient in the intestine-specific homeobox (ISX) transcription factor, which exhibits increased intestinal VA retinoid production from dietary β-carotene (BC). ISX-deficient dams were fed a VA-sufficient or a BC-enriched diet during the last week of gestation and the whole lactation period. Total retinol levels in milk and weanling livers were 2- to 2.5-fold higher in the offspring of BC-fed dams (BC offspring), indicating increased VA supplies during late gestation and lactation. The corresponding VA-sufficient and BC offspring (males and females) were compared at weaning and adulthood after being fed either a standard or high-fat diet (HFD) with regular VA content for 13 weeks from weaning. HFD-induced increases in adiposity metrics, such as fat depot mass and adipocyte diameter, were more pronounced in males than females and were attenuated or suppressed in the BC offspring. Notably, the BC offspring were protected from HFD-induced increases in circulating triacylglycerol levels and hepatic steatosis. These protective effects were associated with reduced food efficiency, enhanced capacity for thermogenesis and mitochondrial oxidative metabolism in adipose tissues, and increased adipocyte hyperplasia rather than hypertrophy in the BC offspring. In conclusion, maternal VA nutrition influenced by genetics may confer metabolic benefits to the offspring, with mild increases in late gestation and lactation protecting against obesity and metabolic dysregulation in adulthood.<b>NEW & NOTEWORTHY</b> A genetic mouse model, deficient in intestine-specific homeobox (ISX) transcription factor, is used to show that a mildly increased maternal vitamin A supply from β-carotene feeding during late gestation and lactation programs energy and lipid metabolism in tissues and protects the offspring from diet-induced hypertrophic obesity and hepatic steatosis. This knowledge may have implications for human populations where polymorphisms in ISX and ISX target genes involved in vitamin A homeostasis are prevalent.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625685","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":"Bruton's tyrosine kinase (BTK) inhibitors alter blood glucose and insulin in obese mice but reduce inflammation independent of BTK.","authors":"Darryl Y Chan, Nicole G Barra, Han Fang, Rodrigo Rodrigues E-Lacerda, Jonathan D Schertzer","doi":"10.1152/ajpendo.00205.2024","DOIUrl":"10.1152/ajpendo.00205.2024","url":null,"abstract":"<p><p>Obesity is associated with metabolic inflammation, which can contribute to insulin resistance, higher blood glucose, and higher insulin indicative of prediabetes progression. The nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a metabolic danger sensor implicated in metabolic inflammation. Many features of metabolic disease can activate the NLRP3 inflammasome; however, it is not yet clear which upstream triggers to target, and there are no clinically approved NLRP3 inflammasome inhibitors for metabolic disease. Bruton's tyrosine kinase (BTK) mediates activation of the NLRP3 inflammasome. Ibrutinib is the most-studied pharmacological inhibitor of BTK, and it can improve blood glucose control in obese mice. However, inhibitors of tyrosine kinases are permissive, and it is unknown if BTK inhibitors require BTK to alter endocrine control of metabolism or metabolic inflammation. We tested whether ibrutinib and acalabrutinib, a new generation BTK inhibitor with higher selectivity, require BTK to inhibit the NLRP3 inflammasome, metabolic inflammation, and blood glucose in obese mice. Chronic ibrutinib administration lowered fasting blood glucose and improved glycemia, whereas acalabrutinib increased fasting insulin levels and increased markers of insulin resistance in high-fat diet-fed CBA/J mice with intact <i>Btk</i>. These metabolic effects of BTK inhibitors were absent in CBA/CaHN-Btk^xid/J mice with mutant <i>Btk</i>. However, ibrutinib and acalabrutinib reduced NF-κB activity, proinflammatory gene expression, and NLRP3 inflammasome activation in macrophages with and without functional BTK. These data highlight that the BTK inhibitors can have divergent effects on metabolism and separate effects on metabolic inflammation that can occur independently of actions on BTK.<b>NEW & NOTEWORTHY</b> Bruton's tyrosine kinase (BTK) is involved in immune function. It was thought that BTK inhibitors improve characteristics of obesity-related metabolic disease by lowering metabolic inflammation. However, tyrosine kinase inhibitors are permissive, and it was not known if different BTK inhibitors alter host metabolism or immunity through actions on BTK. We found that two BTK inhibitors had divergent effects on blood glucose and insulin via BTK, but inhibition of metabolic inflammation occurred independently of BTK in obese mice.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625682","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 role of FGF19 in metabolic regulation: insights from preclinical models to clinical trials.","authors":"Marcela Botelho de Carvalho, Gabriel Machado Chavez Passos Jorge, Luiza Wolf Zanardo, Leticia Miho Hamada, Larissa Dos Santos Izabel, Sergio Santoro, Juliana Magdalon","doi":"10.1152/ajpendo.00156.2024","DOIUrl":"10.1152/ajpendo.00156.2024","url":null,"abstract":"<p><p>Fibroblast growth factor 19 (FGF19) is a hormone synthesized in enterocytes in response to bile acids. This review explores the pivotal role of FGF19 in metabolism, addressing the urgent global health concern of obesity and its associated pathologies, notably type 2 diabetes. The intriguing inverse correlation between FGF19 and body mass or visceral adiposity, as well as its rapid increase following bariatric surgery, emphasizes its potential as a therapeutic target. This article meticulously examines the impact of FGF19 on metabolism by gathering evidence primarily derived from studies conducted in animal models or cell lines, using both FGF19 treatment and genetic modifications. Overall, these studies demonstrate that FGF19 has antidiabetic and antiobesogenic effects. A thorough examination across metabolic tissues, including the liver, adipose tissue, skeletal muscle, and the central nervous system, is conducted, unraveling the intricate interplay of FGF19 across diverse organs. Moreover, we provide a comprehensive overview of clinical trials involving an FGF19 analog called aldafermin, emphasizing promising results in diseases such as nonalcoholic steatohepatitis and diabetes. Therefore, we aim to foster a deeper understanding of FGF19 role and encourage further exploration of its clinical applications, thereby advancing the field and offering innovative approaches to address the escalating global health challenge of obesity and related metabolic conditions.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625686","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}