Lack of Adipocyte AMPK Exacerbates Insulin Resistance and Hepatic Steatosis Through Brown and Beige Adipose Tissue Function

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2016 Jul 14

PMID 27411013

Citations 159

Authors

Emilio P Mottillo

Eric M Desjardins

Justin D Crane

Brennan K Smith

Alex E Green

Serge Ducommun

Tora I Henriksen

Irena A Rebalka

Aida Razi

Kei Sakamoto

Camilla Scheele

Bruce E Kemp

Thomas J Hawke

Joaquin Ortega

James G Granneman

Gregory R Steinberg

Affiliations

Soon will be listed here.

Abstract

Brown (BAT) and white (WAT) adipose tissues play distinct roles in maintaining whole-body energy homeostasis, and their dysfunction can contribute to non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. The AMP-activated protein kinase (AMPK) is a cellular energy sensor, but its role in regulating BAT and WAT metabolism is unclear. We generated an inducible model for deletion of the two AMPK β subunits in adipocytes (iβ1β2AKO) and found that iβ1β2AKO mice were cold intolerant and resistant to β-adrenergic activation of BAT and beiging of WAT. BAT from iβ1β2AKO mice had impairments in mitochondrial structure, function, and markers of mitophagy. In response to a high-fat diet, iβ1β2AKO mice more rapidly developed liver steatosis as well as glucose and insulin intolerance. Thus, AMPK in adipocytes is vital for maintaining mitochondrial integrity, responding to pharmacological agents and thermal stress, and protecting against nutrient-overload-induced NAFLD and insulin resistance.

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