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Cell Metab. 2016 Jul 12;24(1):118-29. doi: 10.1016/j.cmet.2016.06.006.

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

Author information

1
Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St. W., Hamilton, Ontario L8N 3Z5, Canada.
2
Nestlé Institute of Health Sciences SA, EPFL Innovation Park, Lausanne, Switzerland.
3
The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.
4
Department of Pathology and Molecular Medicine, McMaster University, 1280 Main St. W., Hamilton, Ontario L8N 3Z5, Canada.
5
Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main St. W., Hamilton, Ontario L8N 3Z5, Canada.
6
The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen N, Denmark.
7
St Vincent's Institute and Department of Medicine, University of Melbourne, Fitzroy, Victoria 3065, Australia; Mary MacKillop Institute for Health Research Australian Catholic University, Victoria Parade, Fitzroy, Victoria 3065, Australia.
8
Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit 48201, MI, USA.
9
Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St. W., Hamilton, Ontario L8N 3Z5, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main St. W., Hamilton, Ontario L8N 3Z5, Canada. Electronic address: gsteinberg@mcmaster.ca.

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.

PMID:
27411013
PMCID:
PMC5239668
DOI:
10.1016/j.cmet.2016.06.006
[Indexed for MEDLINE]
Free PMC Article

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