Journal
NATURE METABOLISM
Volume 1, Issue 3, Pages 340-349Publisher
NATURE RESEARCH
DOI: 10.1038/s42255-019-0036-9
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Funding
- Medical Research Council UK [MC-A654-5QB10]
- BBSRC-CASE Studentship Award [BB/L502662/1]
- British Heart Foundation
- MRC [MC_U120027537] Funding Source: UKRI
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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(1-3) and is a molecular target of drugs used for the treatment of metabolic diseases, including obesity(4,5). Here we show that mice expressing a gain-of-function AMPK mutant(6) 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.
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