Hematopoietic AMPK ?1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity.

ABSTRACT: Individuals who are obese are frequently insulin resistant, putting them at increased risk of developing type 2 diabetes and its associated adverse health conditions. The accumulation in adipose tissue of macrophages in an inflammatory state is a hallmark of obesity-induced insulin resistance. Here, we reveal a role for AMPK ?1 in protecting macrophages from inflammation under high lipid exposure. Genetic deletion of the AMPK ?1 subunit in mice (referred to herein as ?1(-/-) mice) reduced macrophage AMPK activity, acetyl-CoA carboxylase phosphorylation, and mitochondrial content, resulting in reduced rates of fatty acid oxidation. ?1(-/-) macrophages displayed increased levels of diacylglycerol and markers of inflammation, effects that were reproduced in WT macrophages by inhibiting fatty acid oxidation and, conversely, prevented by pharmacological activation of AMPK ?1-containing complexes. The effect of AMPK ?1 loss in macrophages was tested in vivo by transplantation of bone marrow from WT or ?1(-/-) mice into WT recipients. When challenged with a high-fat diet, mice that received ?1(-/-) bone marrow displayed enhanced adipose tissue macrophage inflammation and liver insulin resistance compared with animals that received WT bone marrow. Thus, activation of AMPK ?1 and increasing fatty acid oxidation in macrophages may represent a new therapeutic approach for the treatment of insulin resistance.

SUBMITTER: Galic S 

PROVIDER: S-EPMC3226000 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature