Lack of Adipocyte AMPK Exacerbates Insulin Resistance and Hepatic Steatosis through Brown and Beige Adipose Tissue Function
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Lack of Adipocyte AMPK Exacerbates Insulin Resistance and Hepatic Steatosis through Brown and Beige Adipose Tissue Function. / Mottillo, Emilio P; Desjardins, Eric M; Crane, Justin D; Smith, Brennan K; Green, Alex E; Ducommun, Serge; Henriksen, Tora I; Rebalka, Irena A; Razi, Aida; Sakamoto, Kei; Schéele, Camilla Charlotte; Kemp, Bruce E; Hawke, Thomas J; Ortega, Joaquin; Granneman, James G; Steinberg, Gregory R.
In: Cell Metabolism, Vol. 24, No. 1, 12.07.2016, p. 118-129.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Lack of Adipocyte AMPK Exacerbates Insulin Resistance and Hepatic Steatosis through Brown and Beige Adipose Tissue Function
AU - Mottillo, Emilio P
AU - Desjardins, Eric M
AU - Crane, Justin D
AU - Smith, Brennan K
AU - Green, Alex E
AU - Ducommun, Serge
AU - Henriksen, Tora I
AU - Rebalka, Irena A
AU - Razi, Aida
AU - Sakamoto, Kei
AU - Schéele, Camilla Charlotte
AU - Kemp, Bruce E
AU - Hawke, Thomas J
AU - Ortega, Joaquin
AU - Granneman, James G
AU - Steinberg, Gregory R
N1 - Copyright © 2016 Elsevier Inc. All rights reserved.
PY - 2016/7/12
Y1 - 2016/7/12
N2 - 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.
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.
KW - Journal Article
U2 - 10.1016/j.cmet.2016.06.006
DO - 10.1016/j.cmet.2016.06.006
M3 - Journal article
C2 - 27411013
VL - 24
SP - 118
EP - 129
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 1
ER -
ID: 166682787