Journal article

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

Sandra Galic, Morgan D Fullerton, Jonathan D Schertzer, Sarah Sikkema, Katarina Marcinko, Carl R Walkley, David Izon, Jane Honeyman, Zhi-Ping Chen, Bryce J van Denderen, Bruce E Kemp, Gregory R Steinberg

JOURNAL OF CLINICAL INVESTIGATION | AMER SOC CLINICAL INVESTIGATION INC | Published : 2011

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 β1 in protecting macrophages from inflammation under high lipid exposure. Genetic deletion of the AMPK β1 subunit in mice (referred to herein as β1(-/-) mice) reduced macrophage AMPK activity, acetyl-CoA carboxylase phosphorylation, and mitochondrial content, resulting in reduced rates of fatty acid oxidation. β1(-/-) macrophages displayed increased levels of diacylglyce..

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Grants

Funding Acknowledgements

These studies were supported by grants and fellowships from the National Health and Medical Research Council (to B.E. Kemp and G.R. Steinberg), the Canadian Diabetes Association (CDA), and the Canadian Institutes of Health Research (CIHR) (to G.R. Steinberg). G.R. Steinberg is a Canada Research Chair in Metabolism and Obesity. M.D. Fullerton is a CIHR Banting Postdoctoral Fellow. J.D. Schemer is a DeGroote Academic Fellow (McMaster University) and is supported by a CDA fellowship. We thank Kimberly Hewitt, Deelan Patel, and Palanivel Rengasamy for technical assistance and Chantal Saab of the McMaster Centre for Translational Imaging for completing the CT analysis.