Adipose TET proteins suppress browning and energy expenditure by epigenetic suppression of Parkin-mediated mitophagy

Parkin-mediated mitophagy is down-regulated in thermogenic activation including WAT browning and BAT activation, but the molecular mechanism of Parkin regulating remains poorly understood. Ten-eleven translocation (TET) proteins catalyze the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine and further oxidized derivatives.

Here we show that TET proteins act as an epigenetic activator of Parkin in adipocytes, thereby regulating adipocyte thermogenesis and systemic energy expenditure in cold-induced thermogenesis. Adipose Tet expression decreases upon cold or adrenergic stimulation. Depleting TET proteins in vivo leads to an elevated expression of thermogenic genes in both white and brown adipose tissues.