Joseph Adkins-Jablonsky, Alexander Tate Lasher, Amit Patki, Akash Nagarajan, Liou Y. Sun
{"title":"生长激素释放激素缺乏症可延长寿命,并在中后期高脂肪喂养期间提高代谢恢复能力。","authors":"Joseph Adkins-Jablonsky, Alexander Tate Lasher, Amit Patki, Akash Nagarajan, Liou Y. Sun","doi":"10.1111/acel.14238","DOIUrl":null,"url":null,"abstract":"<p>Growth hormone-releasing hormone-deficient (GHRH-KO) mice have previously been characterized by lower body weight, disproportionately high body fat accumulation, preferential metabolism of lipids compared to carbohydrates, improved insulin sensitivity, and an extended lifespan. That these mice are long-lived and insulin-sensitive conflicts with the notion that adipose tissue accumulation drives the health detriments associated with obesity (i.e., diabetes), and indicates that GH signaling may be necessary for the development of adverse effects linked to obesity. This prompts investigation into the ultimate effect of diet-induced obesity on the lifespan of these long-lived mice. To this end, we initiated high-fat feeding in mid and late-life in GHRH-KO and wild-type (WT) mice. We carried out extensive lifespan analysis coupled with glucose/insulin tolerance testing and indirect calorimetry to gauge the metabolic effect of high-fat dietary stress through adulthood on these mice. We show that under high-fat diet (HFD) conditions, GHRH-KO mice display extended lifespans relative to WT controls. We also show that GHRH-KO mice are more insulin-sensitive and display less dramatic changes in their metabolism relative to WT mice, with GHRH-KO mice fed HFD displaying respiratory exchange ratios and glucose oxidation rates comparable to control-diet fed GHRH-KO mice, while WT mice fed HFD showed significant reductions in these parameters. Our results indicate that GH deficiency protects against the adverse effects of diet-induced obesity in later life.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8000,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14238","citationCount":"0","resultStr":"{\"title\":\"Growth hormone-releasing hormone deficiency confers extended lifespan and metabolic resilience during high-fat feeding in mid and late life\",\"authors\":\"Joseph Adkins-Jablonsky, Alexander Tate Lasher, Amit Patki, Akash Nagarajan, Liou Y. Sun\",\"doi\":\"10.1111/acel.14238\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Growth hormone-releasing hormone-deficient (GHRH-KO) mice have previously been characterized by lower body weight, disproportionately high body fat accumulation, preferential metabolism of lipids compared to carbohydrates, improved insulin sensitivity, and an extended lifespan. That these mice are long-lived and insulin-sensitive conflicts with the notion that adipose tissue accumulation drives the health detriments associated with obesity (i.e., diabetes), and indicates that GH signaling may be necessary for the development of adverse effects linked to obesity. This prompts investigation into the ultimate effect of diet-induced obesity on the lifespan of these long-lived mice. To this end, we initiated high-fat feeding in mid and late-life in GHRH-KO and wild-type (WT) mice. We carried out extensive lifespan analysis coupled with glucose/insulin tolerance testing and indirect calorimetry to gauge the metabolic effect of high-fat dietary stress through adulthood on these mice. We show that under high-fat diet (HFD) conditions, GHRH-KO mice display extended lifespans relative to WT controls. We also show that GHRH-KO mice are more insulin-sensitive and display less dramatic changes in their metabolism relative to WT mice, with GHRH-KO mice fed HFD displaying respiratory exchange ratios and glucose oxidation rates comparable to control-diet fed GHRH-KO mice, while WT mice fed HFD showed significant reductions in these parameters. Our results indicate that GH deficiency protects against the adverse effects of diet-induced obesity in later life.</p>\",\"PeriodicalId\":55543,\"journal\":{\"name\":\"Aging Cell\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":7.8000,\"publicationDate\":\"2024-06-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14238\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Aging Cell\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/acel.14238\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Biochemistry, Genetics and Molecular Biology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Aging Cell","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/acel.14238","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
Growth hormone-releasing hormone deficiency confers extended lifespan and metabolic resilience during high-fat feeding in mid and late life
Growth hormone-releasing hormone-deficient (GHRH-KO) mice have previously been characterized by lower body weight, disproportionately high body fat accumulation, preferential metabolism of lipids compared to carbohydrates, improved insulin sensitivity, and an extended lifespan. That these mice are long-lived and insulin-sensitive conflicts with the notion that adipose tissue accumulation drives the health detriments associated with obesity (i.e., diabetes), and indicates that GH signaling may be necessary for the development of adverse effects linked to obesity. This prompts investigation into the ultimate effect of diet-induced obesity on the lifespan of these long-lived mice. To this end, we initiated high-fat feeding in mid and late-life in GHRH-KO and wild-type (WT) mice. We carried out extensive lifespan analysis coupled with glucose/insulin tolerance testing and indirect calorimetry to gauge the metabolic effect of high-fat dietary stress through adulthood on these mice. We show that under high-fat diet (HFD) conditions, GHRH-KO mice display extended lifespans relative to WT controls. We also show that GHRH-KO mice are more insulin-sensitive and display less dramatic changes in their metabolism relative to WT mice, with GHRH-KO mice fed HFD displaying respiratory exchange ratios and glucose oxidation rates comparable to control-diet fed GHRH-KO mice, while WT mice fed HFD showed significant reductions in these parameters. Our results indicate that GH deficiency protects against the adverse effects of diet-induced obesity in later life.
期刊介绍:
Aging Cell, an Open Access journal, delves into fundamental aspects of aging biology. It comprehensively explores geroscience, emphasizing research on the mechanisms underlying the aging process and the connections between aging and age-related diseases.