Figure 6. Proposed mechanism by which MPC inhibition induces lipid cycling and the activation of the malate‐aspartate shuttle.

Inhibition of mitochondrial pyruvate import in brown adipocytes results in the induction of lipolysis, a shift toward fatty acid utilization and an increase in energy expenditure. The increase in ATP demand by is a consequence of the activation of lipid cycling, involving a recurrent cycle of fatty acid release and re‐esterification. To support fatty acid oxidation in the absence of pyruvate import, the TCA cycle relies on carbons from glutamine and the activation of the malate‐aspartate shuttle. Thus blocking mitochondrial pyruvate import can promote an increase in energy wasting even in the absence of adrenergic stimulation. LD, lipid droplet; MPC, mitochondrial pyruvate carrier; CPT1, Carnitine Palmitoyltransferase1; ATP, adenosine triphosphate; AMP, adenosine monophosphate; OGC1, oxoglutarate carrier 1; Aralar, mitochondrial aspartate‐glutamate carrier.