Stephan Wueest, Chiara Scaffidi, Pim P. van Krieken, Nils K. Konrad, Christian Koch, Michael S. F. Wiedemann, Anne Goergen, Marcela Borsigova, Ioannis G. Lempesis, Jonas Fullin, Konstantinos N. Manolopoulos, Steffen Böttcher, Gijs H. Goossens, Matthias Blüher, Daniel Konrad
{"title":"脂肪细胞中 Fas(CD95)的表达是饮食诱发肥胖的原因之一。","authors":"Stephan Wueest, Chiara Scaffidi, Pim P. van Krieken, Nils K. Konrad, Christian Koch, Michael S. F. Wiedemann, Anne Goergen, Marcela Borsigova, Ioannis G. Lempesis, Jonas Fullin, Konstantinos N. Manolopoulos, Steffen Böttcher, Gijs H. Goossens, Matthias Blüher, Daniel Konrad","doi":"10.1002/oby.24092","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>Induction of browning in white adipose tissue (WAT) increases energy expenditure and may be an attractive target for the treatment of obesity. Since activation of Fas (CD95) induces pathways known to blunt expression of uncoupling protein 1 (UCP1), we hypothesized that Fas expression in adipocytes inhibits WAT browning and thus contributes to the development of obesity.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Adipocyte-specific Fas knockout (Fas<sup>Δadipo</sup>) and control littermate (Fas<sup>F/F</sup>) mice were fed a regular chow diet or a high-fat diet (HFD) for 20 weeks. Energy expenditure was assessed by indirect calorimetry, and browning was determined in subcutaneous WAT. In vitro, UCP1 was analyzed in subcutaneous murine adipocytes treated with or without Fas ligand. Moreover, <i>FAS</i> expression in WAT was correlated to <i>UCP1</i> and percentage of body fat in human individuals.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>HFD-fed Fas<sup>Δadipo</sup> mice displayed reduced body weight gain and blunted adiposity compared to control littermates. Concomitantly, whole-body energy expenditure and WAT browning were elevated. In cultured adipocytes, Fas ligand treatment blunted isoproterenol-induced UCP1 protein levels. In support of these findings in rodents, <i>FAS</i> expression in WAT correlated negatively with <i>UCP1</i> but positively with adiposity in human individuals.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Fas activation in adipocytes contributes to HFD-associated adiposity in rodents and may be a therapeutic target to reduce obesity and associated diseases.</p>\n </section>\n </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24092","citationCount":"0","resultStr":"{\"title\":\"Fas (CD95) expression in adipocytes contributes to diet-induced obesity\",\"authors\":\"Stephan Wueest, Chiara Scaffidi, Pim P. van Krieken, Nils K. Konrad, Christian Koch, Michael S. F. Wiedemann, Anne Goergen, Marcela Borsigova, Ioannis G. Lempesis, Jonas Fullin, Konstantinos N. Manolopoulos, Steffen Böttcher, Gijs H. Goossens, Matthias Blüher, Daniel Konrad\",\"doi\":\"10.1002/oby.24092\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>Induction of browning in white adipose tissue (WAT) increases energy expenditure and may be an attractive target for the treatment of obesity. Since activation of Fas (CD95) induces pathways known to blunt expression of uncoupling protein 1 (UCP1), we hypothesized that Fas expression in adipocytes inhibits WAT browning and thus contributes to the development of obesity.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Adipocyte-specific Fas knockout (Fas<sup>Δadipo</sup>) and control littermate (Fas<sup>F/F</sup>) mice were fed a regular chow diet or a high-fat diet (HFD) for 20 weeks. Energy expenditure was assessed by indirect calorimetry, and browning was determined in subcutaneous WAT. In vitro, UCP1 was analyzed in subcutaneous murine adipocytes treated with or without Fas ligand. Moreover, <i>FAS</i> expression in WAT was correlated to <i>UCP1</i> and percentage of body fat in human individuals.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>HFD-fed Fas<sup>Δadipo</sup> mice displayed reduced body weight gain and blunted adiposity compared to control littermates. Concomitantly, whole-body energy expenditure and WAT browning were elevated. In cultured adipocytes, Fas ligand treatment blunted isoproterenol-induced UCP1 protein levels. In support of these findings in rodents, <i>FAS</i> expression in WAT correlated negatively with <i>UCP1</i> but positively with adiposity in human individuals.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>Fas activation in adipocytes contributes to HFD-associated adiposity in rodents and may be a therapeutic target to reduce obesity and associated diseases.</p>\\n </section>\\n </div>\",\"PeriodicalId\":215,\"journal\":{\"name\":\"Obesity\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2024-07-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24092\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Obesity\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/oby.24092\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Obesity","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/oby.24092","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Fas (CD95) expression in adipocytes contributes to diet-induced obesity
Objective
Induction of browning in white adipose tissue (WAT) increases energy expenditure and may be an attractive target for the treatment of obesity. Since activation of Fas (CD95) induces pathways known to blunt expression of uncoupling protein 1 (UCP1), we hypothesized that Fas expression in adipocytes inhibits WAT browning and thus contributes to the development of obesity.
Methods
Adipocyte-specific Fas knockout (FasΔadipo) and control littermate (FasF/F) mice were fed a regular chow diet or a high-fat diet (HFD) for 20 weeks. Energy expenditure was assessed by indirect calorimetry, and browning was determined in subcutaneous WAT. In vitro, UCP1 was analyzed in subcutaneous murine adipocytes treated with or without Fas ligand. Moreover, FAS expression in WAT was correlated to UCP1 and percentage of body fat in human individuals.
Results
HFD-fed FasΔadipo mice displayed reduced body weight gain and blunted adiposity compared to control littermates. Concomitantly, whole-body energy expenditure and WAT browning were elevated. In cultured adipocytes, Fas ligand treatment blunted isoproterenol-induced UCP1 protein levels. In support of these findings in rodents, FAS expression in WAT correlated negatively with UCP1 but positively with adiposity in human individuals.
Conclusions
Fas activation in adipocytes contributes to HFD-associated adiposity in rodents and may be a therapeutic target to reduce obesity and associated diseases.
期刊介绍:
Obesity is the official journal of The Obesity Society and is the premier source of information for increasing knowledge, fostering translational research from basic to population science, and promoting better treatment for people with obesity. Obesity publishes important peer-reviewed research and cutting-edge reviews, commentaries, and public health and medical developments.