Uncoupling of Metabolic Health from Longevity through Genetic Alteration of Adipose Tissue Lipid-Binding Proteins.
Uncoupling of Metabolic Health from Longevity through Genetic Alteration of Adipose Tissue Lipid-Binding Proteins.
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DOI：
10.1016/j.celrep.2017.09.051
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发表时间：
2017-10-10
期刊：
影响因子：
8.8
通讯作者：
Hotamisligil GS
中科院分区：
文献类型：
--
作者：
Charles KN;Li MD;Engin F;Arruda AP;Inouye K;Hotamisligil GS
代谢健康的恶化是衰老的标志，通常被认为对长寿有害。高热量饮食会损害新陈代谢，加速衰老；相反，热量限制（CR）可以预防与年龄相关的代谢疾病，延长寿命。然而，尚不清楚保持代谢健康是否足以延长寿命。我们利用缺乏Fabp4/5的遗传小鼠模型来解决这个问题，该模型具有保护代谢疾病的功能，并且与CR具有相同的分子和脂质组学特征。fabp4缺陷小鼠表现出较长的代谢健康跨度，可防止胰岛素抵抗和葡萄糖耐受不良、炎症、脂肪组织完整性恶化和脂肪肝疾病。然而，令人惊讶的是，缺乏fabp的小鼠没有表现出任何寿命延长。这些数据表明，在没有CR的情况下，代谢健康期的延长可以与寿命分离，表明这些途径的独立驱动因素的潜力，至少在实验室小鼠中是这样。代谢健康的恶化是衰老的标志，被认为对长寿有害。Charles等人利用fabp缺陷小鼠作为模型，证明在该模型中，即使在代谢应激下，代谢健康的保存也会持续一生，但不会导致长寿。
Deterioration of metabolic health is a hallmark of aging and generally assumed to be detrimental to longevity. Exposure to a high-calorie diet impairs metabolism and accelerates aging; conversely, calorie restriction (CR) prevents age-related metabolic diseases and extends lifespan. However, it is unclear whether preservation of metabolic health is sufficient to extend lifespan. We utilized a genetic mouse model lacking Fabp4/5 that confers protection against metabolic diseases and shares molecular and lipidomic features with CR to address this question. Fabp4-deficient mice exhibit extended metabolic healthspan with protection against insulin resistance and glucose intolerance, inflammation, deterioration of adipose tissue integrity, and fatty liver disease. Surprisingly, however, Fabp-deficient mice did not exhibit any extension of lifespan. These data indicate that extension of metabolic healthspan in the absence of CR can be uncoupled from lifespan, indicating the potential for independent drivers of these pathways, at least in laboratory mice. Deterioration of metabolic health is a hallmark of aging and thought to be detrimental to longevity. Charles et al. utilize FABP-deficient mice as a model to demonstrate that the preservation of metabolic health in this model persists throughout life even under metabolic stress, but does not lead to longevity.
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影响因子：
64.5
作者：
Cao H;Gerhold K;Mayers JR;Wiest MM;Watkins SM;Hotamisligil GS
通讯作者：
Hotamisligil GS
影响因子：
16.2
作者：
Gerstein, Hertzel C.;Beavers, Daniel P.;Friedewald, William T.
通讯作者：
Friedewald, William T.
影响因子：
17.1
作者：
Burak, M. Furkan;Inouye, Karen E.;Hotamisligil, Goekhan S.
通讯作者：
Hotamisligil, Goekhan S.
DOI：
10.1002/hep.24713
发表时间：
2012-02
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Gregg SQ;Gutiérrez V;Robinson AR;Woodell T;Nakao A;Ross MA;Michalopoulos GK;Rigatti L;Rothermel CE;Kamileri I;Garinis GA;Stolz DB;Niedernhofer LJ
通讯作者：
Niedernhofer LJ
DOI：
10.1016/j.tem.2009.11.005
发表时间：
2010-03
期刊：
Trends in endocrinology and metabolism: TEM
影响因子：
--
作者：
Anderson RM;Weindruch R
通讯作者：
Weindruch R