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

Author: Pollard, A.E.; Martins, L.; Muckett, P.J.; Khadayate, S.; Bornot, A.; Clausen, M.; Admyre, T.; Bjursell, M.; Fiadeiro, R.; Wilson, L.; Whilding, C.; Kotiadis, V.N.; Duchen, M.R.; Sutton, D.; Penfold, L.; Sardini, A.; Bohlooly-Y, M.; Smith, D.M.; Read, J.A.; Snowden, M.A.; Woods, A.; Carling, D.

Description: 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 homeostasis and is a molecular target of drugs used for the treatment of metabolic diseases, including obesity. Here we show that mice expressing a gain-of-function AMPK mutant 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.

Subject headings: Obesity, Energy intake; Energy output; Humans; AMPK

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

Publication year: 2019

Journal or book title: Nature Metabolism

Volume: 1

Issue: 3

Pages: 340-349

Find the full text : https://www.nature.com/articles/s42255-019-0036-9

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Type: Journal Article

Serial number: 2864