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

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 Charlotte Schéele; Bruce E Kemp; Thomas J Hawke; Joaquin Ortega; James G Granneman; Gregory R Steinberg

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

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 Charlotte Schéele, Bruce E Kemp, Thomas J Hawke, Joaquin Ortega, James G Granneman, Gregory R Steinberg

Department of Clinical Medicine

138 Citations (Scopus)

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.

Original language	English
Journal	Cell Metabolism
Volume	24
Issue number	1
Pages (from-to)	118-129
Number of pages	12
ISSN	1550-4131
DOIs	https://doi.org/10.1016/j.cmet.2016.06.006
Publication status	Published - 12 Jul 2016

Keywords

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cmet.2016.06.006

http://www.cell.com/article/S1550413116302923/pdf

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Mottillo, E. P., Desjardins, E. M., Crane, J. D., Smith, B. K., Green, A. E., Ducommun, S., Henriksen, T. I., Rebalka, I. A., Razi, A., Sakamoto, K., Schéele, C. C., Kemp, B. E., Hawke, T. J., Ortega, J., Granneman, J. G., & Steinberg, G. R. (2016). Lack of Adipocyte AMPK Exacerbates Insulin Resistance and Hepatic Steatosis through Brown and Beige Adipose Tissue Function. Cell Metabolism, 24(1), 118-129. https://doi.org/10.1016/j.cmet.2016.06.006

Mottillo, EP, Desjardins, EM, Crane, JD, Smith, BK, Green, AE, Ducommun, S, Henriksen, TI, Rebalka, IA, Razi, A, Sakamoto, K, Schéele, CC, Kemp, BE, Hawke, TJ, Ortega, J, Granneman, JG & Steinberg, GR 2016, 'Lack of Adipocyte AMPK Exacerbates Insulin Resistance and Hepatic Steatosis through Brown and Beige Adipose Tissue Function', Cell Metabolism, vol. 24, no. 1, pp. 118-129. https://doi.org/10.1016/j.cmet.2016.06.006

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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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AU - Smith, Brennan K

AU - Green, Alex E

AU - Ducommun, Serge

AU - Henriksen, Tora I

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AU - Razi, Aida

AU - Sakamoto, Kei

AU - Schéele, Camilla Charlotte

AU - Kemp, Bruce E

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AU - Ortega, Joaquin

AU - Granneman, James G

AU - Steinberg, Gregory R

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

Abstract

Keywords

UN SDGs

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