ABSTRACT
Brown adipose tissue plays a significant role in ameliorating obesity and other metabolic disorders, and skeletal muscle is a highly adaptable tissue that is essential for maintaining whole-body energy homeostasis. The identification and functional characterization of DNA demethylation machinery established important roles of the ten-eleven (TET) translocation family in epigenetic reprogramming. Brown adipocytes and myoblasts are derived from a common progenitor (myogenic factor 5 (Myf5)-expressing cells) and Tet genes control DNA demethylation during myoblast differentiation. Here we show the role of TET proteins in regulating skeletal muscles fiber switch and energy homeostasis. Ablation of Tet family genes in Myf5-expressing progenitor cells promotes glycolytic muscle fibers while appears to be dispensable in brown adipocyte lineage determination. These Tet-deficient mice have increased energy expenditure during high fat diet feeding and are protected from diet-induced obesity. Thus, TET family proteins are important factors in regulating muscle fiber type specificity and whole-body energy homeostasis.