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AMPK activation protects against diet induced obesity through Ucp1-independent thermogenesis in subcutaneous white adipose tissue

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Title: AMPK activation protects against diet induced obesity through Ucp1-independent thermogenesis in subcutaneous white adipose tissue
Authors: Pollard, AE
Martins, L
Muckett, PJ
Khadayate, S
Bornot, A
Clausen, M
Admyre, T
Bjursell, M
Fiadeiro, R
Wilson, L
Whilding, C
Kotiadis, VN
Duchen, MR
Sutton, D
Penfold, L
Sardini, A
Bohlooly-Y, M
Smith, DM
Read, JA
Snowden, MA
Woods, A
Carling, D
Item Type: Journal Article
Abstract: Obesity results from a chronic imbalance between energy intake and energy output but remains difficult to prevent or treat in humans. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is an important regulator of energy homeostasis1,2,3 and is a molecular target of drugs used for the treatment of metabolic diseases, including obesity4,5. Here we show that mice expressing a gain-of-function AMPK mutant6 display a change in morphology of subcutaneous white adipocytes that is reminiscent of browning. However, despite a dramatic increase in mitochondrial content, Ucp1 expression is undetectable in these adipocytes. In response to a high-fat diet (HFD), expression of skeletal muscle–associated genes is induced in subcutaneous white adipocytes from the gain-of-function AMPK mutant mice. Chronic genetic AMPK activation results in protection against diet-induced obesity due to an increase in whole-body energy expenditure, most probably because of a substantial increase in the oxygen consumption rate of white adipose tissue. These results suggest that AMPK activation enriches, or leads to the emergence of, a population of subcutaneous white adipocytes that produce heat via Ucp1-independent uncoupling of adenosine triphosphate (ATP) production on a HFD. Our findings indicate that AMPK activation specifically in adipose tissue may have therapeutic potential for the treatment of obesity.
Issue Date: 1-Mar-2019
Date of Acceptance: 17-Jan-2019
URI: http://hdl.handle.net/10044/1/69486
DOI: https://dx.doi.org/10.1038/s42255-019-0036-9
ISSN: 2522-5812
Publisher: Nature Research
Start Page: 340
End Page: 349
Journal / Book Title: Nature Metabolism
Volume: 1
Issue: 3
Copyright Statement: © 2019 Springer Nature Publishing AG
Publication Status: Published
Conference Place: England
Embargo Date: 2019-08-25
Online Publication Date: 2019-02-25
Appears in Collections:Clinical Sciences
Molecular Sciences
Faculty of Medicine



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