Thioesterase superfamily member 1 (Them1), a BAT-enriched long chain fatty acyl-CoA thioesterase, is upregulated by cold and downregulated by warm ambient temperatures. Them1 (-/-) mice exhibit increased energy expenditure and resistance to diet-induced obesity and diabetes, but the mechanistic contribution of Them1 to the regulation of cold thermogenesis remains unknown. Them1 may act as a break on uncontrolled heat production and limit the extent of energy expenditure. Pharmacologic inhibition of Them1 could provide a targeted strategy for the management of metabolic disorders via activation of brown fat.
PC-TP
Phosphatidylcholine transfer protein (PC-TP, synonym StARD2) binds phosphatidylcholines, and catalyzes their intermembrane transfer and exchange in vitro. The structure of PC-TP comprises a hydrophobic pocket and a well-defined head group binding site, and its gene expression is regulated by peroxisome proliferator activated receptor-alpha. Recent studies have revealed key regulatory roles for PC-TP in lipid and glucose metabolism. Notably, Pctp(-/-) mice are sensitized to the action of insulin, and exhibit more efficient brown fat-mediated thermogenesis. PC-TP appears to limit access of fatty acids to mitochondria by stimulating the activity of thioesterase superfamily member 2, a newly characterized long-chain fatty acyl-coenzyme A thioesterase. Because PC-TP discriminates between phosphatidylcholines within lipid bilayers, it might function as a sensor that links metabolic regulation to membrane composition.