Brown adipocytes are specialized to dissipate chemical energy as heat and are associated with improved metabolic phenotypes. Herein we demonstrate that pyruvate kinase M2 (PKM2) is expressed in brown and white adipose depots. shRNA-mediated depletion of PKM2 in white preadipocytes promotes the development of a brown fat-like thermogenic program. Reconstitution of knockdown cells with PKM2 abrogates thermogenic gene induction that is caused by PKM2 deficiency. In addition, metabolomic profiling of PKM2 deficiency revealed notable metabolic similarities with bona fide brown adipocytes. Importantly, PKM2 deficiency in white adipocytes increases ATP turnover, and enhances basal and maximal mitochondrial respiration. Notably, subcutaneous injection of PKM2-deficient preadipocytes into mice (following established protocols) gives rise to ectopic fat pads with morphological and biochemical characteristics of brown adipocytes with enhanced glucose uptake in vivo. Collectively, these findings identify PKM2 as a novel component of the molecular circuit that contributes to adipocyte plasticity and adaptive thermogenesis, which may have potential therapeutic implications.
The Royal Society (ME 2012) (2012) Proc Physiol Soc 29, C08 and PC08
Research Symposium: Pyruvate kinase M2 deficiency promotes a brown fat-like program in white adipocytes
A. Bettaieb1, J. Bakke1, N. Nagata1, A. Tomilov1, C. Lyssiotis2, J. Asara2, G. Cortopassi1, L. Cantley2, F. G. Haj1
1. Nutrition and Internal Medicine, University of California Davis, Davis, California, United States. 2. Systems Biology, Harvard Medical School, Boston, Massachusetts, United States.
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Where applicable, experiments conform with Society ethical requirements.