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Article: Calorie Restriction Prevents Metabolic Aging Caused by Abnormal SIRT1 Function in Adipose Tissues

TitleCalorie Restriction Prevents Metabolic Aging Caused by Abnormal SIRT1 Function in Adipose Tissues
Authors
Issue Date2015
Citation
Diabetes, 2015, v. 64, p. 1576-1590 How to Cite?
AbstractAdipose tissue is a pivotal organ determining longevity, due largely to its role in maintaining whole body energy homeostasis and insulin sensitivity. SIRT1 is a NAD-dependent protein deacetylase possessing anti-ageing activities in a wide range of organisms. The present study demonstrates that mice with adipose tissue-selective overexpression of hSIRT1(H363Y), a dominant negative mutant that disrupts endogenous SIRT1 activity, show accelerated development of metabolic ageing. These mice, referred to as Adipo-H363Y, exhibit hyperglycemia, dyslipidemia, ectopic lipid deposition, insulin resistance and glucose intolerance at a much younger age than their wild type littermates. The metabolic defects of Adipo-H363Y are associated with abnormal epigenetic modifications and chromatin remodeling in their adipose tissues, as a result of excess accumulation of biotin, which inhibits endogenous SIRT1 activity, leading to increased inflammation, cellularity and collagen deposition. The enzyme acetyl-CoA carboxylase 2 plays an important role in biotin accumulation within adipose tissues of Adipo-H363Y. Calorie restriction prevents biotin accumulation, abolishes abnormal histone biotinylation, and completely restores the metabolic and adipose functions of Adipo-H363Y. The effects are mimicked by short-term restriction of biotin intake, an approach potentially translatable to humans for maintaining the epigenetic and chromatin remodeling capacity of adipose tissues and preventing ageing-associated metabolic disorders.
Persistent Identifierhttp://hdl.handle.net/10722/209789

 

DC FieldValueLanguage
dc.contributor.authorXu, Cen_US
dc.contributor.authorCAI, Yen_US
dc.contributor.authorFan, Pen_US
dc.contributor.authorBai, Ben_US
dc.contributor.authorCHEN, Jen_US
dc.contributor.authorDeng, Hen_US
dc.contributor.authorChe, CMen_US
dc.contributor.authorXu, Aen_US
dc.contributor.authorVanhoutte, PMGRen_US
dc.contributor.authorWang, Yen_US
dc.date.accessioned2015-05-18T03:23:09Z-
dc.date.available2015-05-18T03:23:09Z-
dc.date.issued2015en_US
dc.identifier.citationDiabetes, 2015, v. 64, p. 1576-1590en_US
dc.identifier.urihttp://hdl.handle.net/10722/209789-
dc.description.abstractAdipose tissue is a pivotal organ determining longevity, due largely to its role in maintaining whole body energy homeostasis and insulin sensitivity. SIRT1 is a NAD-dependent protein deacetylase possessing anti-ageing activities in a wide range of organisms. The present study demonstrates that mice with adipose tissue-selective overexpression of hSIRT1(H363Y), a dominant negative mutant that disrupts endogenous SIRT1 activity, show accelerated development of metabolic ageing. These mice, referred to as Adipo-H363Y, exhibit hyperglycemia, dyslipidemia, ectopic lipid deposition, insulin resistance and glucose intolerance at a much younger age than their wild type littermates. The metabolic defects of Adipo-H363Y are associated with abnormal epigenetic modifications and chromatin remodeling in their adipose tissues, as a result of excess accumulation of biotin, which inhibits endogenous SIRT1 activity, leading to increased inflammation, cellularity and collagen deposition. The enzyme acetyl-CoA carboxylase 2 plays an important role in biotin accumulation within adipose tissues of Adipo-H363Y. Calorie restriction prevents biotin accumulation, abolishes abnormal histone biotinylation, and completely restores the metabolic and adipose functions of Adipo-H363Y. The effects are mimicked by short-term restriction of biotin intake, an approach potentially translatable to humans for maintaining the epigenetic and chromatin remodeling capacity of adipose tissues and preventing ageing-associated metabolic disorders.en_US
dc.languageengen_US
dc.relation.ispartofDiabetesen_US
dc.titleCalorie Restriction Prevents Metabolic Aging Caused by Abnormal SIRT1 Function in Adipose Tissuesen_US
dc.typeArticleen_US
dc.identifier.emailXu, C: xchku@hku.hken_US
dc.identifier.emailBai, B: baibohku@hku.hken_US
dc.identifier.emailDeng, H: hbdeng1@hku.hken_US
dc.identifier.emailChe, CM: cmche@hku.hken_US
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_US
dc.identifier.emailVanhoutte, PMGR: vanhoutt@hku.hken_US
dc.identifier.emailWang, Y: yuwanghk@hku.hken_US
dc.identifier.authorityChe, CM=rp00670en_US
dc.identifier.authorityXu, A=rp00485en_US
dc.identifier.authorityVanhoutte, PMGR=rp00238en_US
dc.identifier.authorityWang, Y=rp00239en_US
dc.identifier.doi10.2337/db14-1180en_US
dc.identifier.hkuros243253en_US
dc.identifier.volume64en_US
dc.identifier.spage1576en_US
dc.identifier.epage1590en_US

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