Deficiency of the lipid synthesis enzyme, DGAT1, extends longevity in mice

被引：34
|
作者：
Streeper, Ryan S. [1 ,2 ]
Grueter, Carrie A. [2 ]
Salomonis, Nathan [2 ]
Cases, Sylvaine [2 ]
Levin, Malin C. [2 ]
Koliwad, Suneil K. [1 ,2 ,4 ]
Zhou, Ping [2 ]
Hirschey, Matthew D. [3 ]
Verdin, Eric [3 ,4 ]
Farese, Robert V., Jr. [1 ,4 ,5 ,6 ]
机构：
[1] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA
[2] Gladstone Inst Cardiovasc Dis, San Francisco, CA USA
[3] Gladstone Inst Virol & Immunol, San Francisco, CA USA
[4] Univ Calif San Francisco, Dept Med, San Francisco, CA USA
[5] Univ Calif San Francisco, Dept Biochem, San Francisco, CA 94143 USA
[6] Univ Calif San Francisco, Dept Biophys, San Francisco, CA 94143 USA
来源：
AGING-US | 2012年 / 4卷 / 01期
关键词：
DGAT1; adipose tissue; longevity; triglycerides; calorie restriction; CALORIC RESTRICTION; OBESITY RESISTANCE; LEPTIN SENSITIVITY; INSULIN-RECEPTOR; GENE-EXPRESSION; LACKING; METABOLISM; LIPOTOXICITY; TISSUE; CELLS;
D O I：
10.18632/aging.100424
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Calorie restriction results in leanness, which is linked to metabolic conditions that favor longevity. We show here that deficiency of the triglyceride synthesis enzyme acyl CoA:diacylglycerol acyltransferase 1 (DGAT1), which promotes leanness, also extends longevity without limiting food intake. Female DGAT1-deficient mice were protected from age-related increases in body fat, tissue triglycerides, and inflammation in white adipose tissue. This protection was accompanied by increased mean and maximal life spans of (similar to)25% and (similar to)10%, respectively. Middle-aged Dgat1(-/-) mice exhibited several features associated with longevity, including decreased levels of circulating insulin growth factor 1 (IGF1) and reduced fecundity. Thus, deletion of DGAT1 in mice provides a model of leanness and extended lifespan that is independent of calorie restriction.
引用
收藏
页码：13 / 27
页数：15
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