Diacylglycerol acyltransferase 2 links glucose utilization to fatty acid oxidation in the brown adipocytes

Abstract

Brown adipose tissue uptake of glucose and fatty acids is very high during nonshivering thermogenesis. Adrenergic stimulation markedly increases glucose uptake, de novo lipogenesis, and FA oxidation simultaneously. The mechanism that enables this concerted response has hitherto been unknown. Here, we find that in primary brown adipocytes and brown adipocyte-derived cell line (IMBAT-1), acute inhibition and longer-term knockdown of DGAT2 links the increased de novo synthesis of fatty acids from glucose to a pool of TAG that is simultaneously hydrolyzed, providing FA for mitochondrial oxidation. DGAT1 does not contribute to this pathway, but uses exogenous FA and glycerol to synthesize a functionally distinct pool of TAG to which DGAT2 also contributes. The DGAT2-dependent channelling of14 C from glucose into TAG and CO2 was reproduced in ô3-agonist-stimulated primary brown adipocytes. Knockdown of DGAT2 in IMBAT-1 affected the mRNA levels of UCP1 and genes important in FA activation and esterification. Therefore, in ô3-agonist activated brown adipocytes, DGAT2 specifically enables channelling of de novo synthesized FA into a rapidly mobilized pool of TAG, which is simultaneously hydrolyzed to provide substrates for mitochondrial fatty acid oxidation.-Irshad, Z., F. Dimitri, M. Christian. and V. A. Zammit. Diacylglycerol acyltransferase 2 links glucose utilization to fatty acid oxidation in the brown adipocytes. J. Lipid Res. 2017. 58: 15-30.