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

Institut for Klinisk Medicin

138 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Cell Metabolism
Vol/bind	24
Udgave nummer	1
Sider (fra-til)	118-129
Antal sider	12
ISSN	1550-4131
DOI	https://doi.org/10.1016/j.cmet.2016.06.006
Status	Udgivet - 12 jul. 2016

FN’s Verdensmål

Dette resultat bidrager til følgende verdensmål

Adgang til dokumentet

10.1016/j.cmet.2016.06.006

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

Citationsformater

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, bind 24, nr. 1, s. 118-129. https://doi.org/10.1016/j.cmet.2016.06.006

@article{a075e361ade14499871abde3d612b9d1,

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

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.",

keywords = "Journal Article",

author = "Mottillo, {Emilio P} and Desjardins, {Eric M} and Crane, {Justin D} and Smith, {Brennan K} and Green, {Alex E} and Serge Ducommun and Henriksen, {Tora I} and Rebalka, {Irena A} and Aida Razi and Kei Sakamoto and Sch{\'e}ele, {Camilla Charlotte} and Kemp, {Bruce E} and Hawke, {Thomas J} and Joaquin Ortega and Granneman, {James G} and Steinberg, {Gregory R}",

year = "2016",

month = jul,

day = "12",

doi = "10.1016/j.cmet.2016.06.006",

language = "English",

volume = "24",

pages = "118--129",

journal = "Cell Metabolism",

issn = "1550-4131",

publisher = "Cell Press",

number = "1",

}

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

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

SN - 1550-4131

VL - 24

SP - 118

EP - 129

JO - Cell Metabolism

JF - Cell Metabolism

IS - 1

ER -

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

Abstract

FN’s Verdensmål

Adgang til dokumentet

Fingeraftryk

Citationsformater