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

Brown adipose tissue uptake of glucose and fatty acids is very high during non-shivering 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 a 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 TG which is simultaneously hydrolysed, providing FA for mitochondrial oxidation. DGAT1 does not contribute to this pathway, but uses exogenous FA and glycerol to synthesise a functionally distinct pool of TG to which DGAT2 also contributes to it. The DGAT2-dependent channelling of 14C from glucose into TG and CO2 was reproduced in β3-agonist-stimulated primary brown adipocytes. Knockdown of DGAT2 in IMBAT-1 affected the mRNA levels of several genes important in FA activation and esterification. Therefore, in β3-agonist activated brown adipocytes, DGAT2 specifically enables channelling of de novo synthesised FA into a rapidly mobilised pool of TG which is simultaneously hydrolysed to provide substrates for mitochondrial fatty acid oxidation.