Recent insights into the molecular mechanisms of simultaneous fatty acid oxidation and synthesis in brown adipocytes

Brown adipocytes is a specialized fat cell that dissipates nutrient-derived chemical energy in the form of heat, instead of ATP synthesis. This unique feature provides a marked capacity for brown adipocyte mitochondria to oxidize substrates independent of ADP availability. Upon cold exposure, brown adipocytes preferentially oxidize free fatty acids (FFA) liberated from triacylglycerol (TAG) in lipid droplets to support thermogenesis. In addition, brown adipocytes take up large amounts of circulating glucose, concurrently increasing glycolysis and de novo FA synthesis from glucose. Given that FA oxidation and glucose-derived FA synthesis are two antagonistic mitochondrial processes in the same cell, it has long been questioned how brown adipocytes run FA oxidation and FA synthesis simultaneously. In this review, I summarize mechanisms regulating mitochondrial substrate selection and describe recent findings of two distinct populations of brown adipocyte mitochondria with different substrate preferences. I further discuss how these mechanisms may permit a concurrent increase in glycolysis, FA synthesis, and FA oxidation in brown adipocytes.

Automated summary

Brown adipocytes are specialized fat cells that dissipate energy as heat instead of ATP synthesis. These cells have the unique ability to oxidize substrates independent of ADP availability and preferentially oxidize free fatty acids released from lipid droplets to produce heat during cold exposure. Additionally, brown adipocytes can take up large amounts of glucose and increase glycolysis and fatty acid synthesis. This review summarizes mechanisms regulating mitochondrial substrate selection and discusses recent findings on two distinct populations of brown adipocyte mitochondria with different substrate preferences. The review further explores how these mechanisms allow for simultaneous increases in glycolysis, fatty acid synthesis, and fatty acid oxidation in brown adipocytes.