Fig. 11.

Proposed pathways that link DGAT2 to de novo fatty acid synthesis and thermogenesis in brown adipocytes. Fatty acids synthesized de novo from glucose (FA’’) are used to form a pool of diglyceride (DG’’) which is esterified with FA’’ by DGAT2 to form a distinct pool of triglyceride (TG’’). Adrenergic (β3) stimulation simultaneously activates de novo lipogenesis and TAG lipolysis. A product of lipolysis activates the process of glucose utilization for lipogenesis (DNL) upon stimulation of the cells by β3-agonists through a positive feedback mechanism which is interrupted by inhibition of ATGL. TAG lipolysis provides FA substrate for uncoupled mitochondrial oxidation. FA activate UCP1, the expression of which is increased by β3-action. Glycerol-3-P synthesized from exogenous glycerol is used for the synthesis of a separate DG pool (DG’) which is used as a substrate for re/esterification preferentially by DGAT1, and to a lesser extent by DGAT2. Glycerol-3-P generated endogenously from glucose is used to form both DG’’ and DG’. Exogenous FA is not oxidized directly, but is re/esterified by DGAT1 or DGAT2 redundantly into/within a larger TAG pool (TAG’) before oxidation.