Perilipin-2-null mice are protected against diet-induced obesity, adipose inflammation, and fatty liver disease

被引:182
作者
McManaman, James L. [1 ,2 ]
Bales, Elise S. [1 ]
Orlicky, David J. [4 ]
Jackman, Matthew [2 ,5 ]
MacLean, Paul S. [2 ,5 ]
Cain, Shannon [2 ]
Crunk, Amanda E. [3 ]
Mansur, Ayla [6 ]
Graham, Christine E. [6 ]
Bowman, Thomas A. [6 ]
Greenberg, Andrew S. [6 ]
机构
[1] Univ Colorado, Sch Med, Div Basic Reprod Sci, Aurora, CO USA
[2] Univ Colorado, Sch Med, Ctr Human Nutr, Aurora, CO USA
[3] Univ Colorado, Sch Med, Grad Program Mol Biol, Aurora, CO USA
[4] Univ Colorado, Sch Med, Dept Pathol, Aurora, CO USA
[5] Univ Colorado, Sch Med, Div Endocrinol & Metab, Aurora, CO USA
[6] Tufts Univ, Jean Mayer US Dept Agr Human Nutr Res Ctr Aging, Boston, MA 02111 USA
基金
美国国家卫生研究院;
关键词
food consumption; metabolism; gene expression; activity; DIFFERENTIATION-RELATED PROTEIN; DROPLET-ASSOCIATED PROTEIN; LIPID DROPLETS; HEPATIC STEATOSIS; NONALCOHOLIC STEATOHEPATITIS; INSULIN-RESISTANCE; ADIPOCYTE DEATH; MAMMARY-GLANDS; ADIPOPHILIN; HEPATOCYTE;
D O I
10.1194/jlr.M035063
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The cytoplasmic lipid droplet (CLD) protein perilipin-2 (Plin2) is expressed in multiple nonadipose tissues, where it is thought to play a role in regulating their lipid storage properties. However, the extent to which Plin2 functions in nutrient utilization and metabolism, or how it influences the consequences of over-feeding, remains unclear. In this study, we demonstrate that the absence of Plin2 prevents high-fat diet(HFD)-induced obesity in male and female mice. This response is associated with increased formation of subcutaneous beige adipocyte cells with uncoupling protein 1 expression, and amelioration of inflammatory foci formation in white adipose tissue and steatosis in the liver. Experiments demonstrate that Plin2 loss results in reduced energy intake and increased physical activity in response to HFD feeding. Our study provides the first evidence that Plin2 contributes to HFD-induced obesity by modulating food intake, and that its absence prevents obesity-associated adipose tissue inflammatory foci and liver steatosis.-McManaman, J. L., E. S. Bales, D. J. Orlicky, M. Jackman, P. S. MacLean, S. Cain, A. E. Crunk, A. Mansur, C. E. Graham, T. A. Bowman, and A. S. Greenberg. Perilipin-2-null mice are protected against diet-induced obesity, adipose inflammation, and fatty liver disease. J. Lipid Res. 2013. 54: 1346-1359.
引用
收藏
页码:1346 / 1359
页数:14
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