Grp78 heterozygosity promotes adaptive unfolded protein response and attenuates diet-induced obesity and insulin resistance.

ABSTRACT:

Objective

To investigate the role of the endoplasmic reticulum (ER) chaperone glucose-regulated protein (GRP) 78/BiP in the pathogenesis of obesity, insulin resistance, and type 2 diabetes.

Research design and methods

Male Grp78(+/-) mice and their wild-type littermates were subjected to a high-fat diet (HFD) regimen. Pathogenesis of obesity and type 2 diabetes was examined by multiple approaches of metabolic phenotyping. Tissue-specific insulin sensitivity was analyzed by hyperinsulinemic-euglycemic clamps. Molecular mechanism was explored via immunoblotting and tissue culture manipulation.

Results

Grp78 heterozygosity increases energy expenditure and attenuates HFD-induced obesity. Grp78(+/-) mice are resistant to diet-induced hyperinsulinemia, liver steatosis, whit

SUBMITTER: Ye R 

PROVIDER: S-EPMC2797945 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature