β-adrenergic receptor-stimulated lipolysis requires the RAB7-mediated autolysosomal lipid degradation

Abstract

Hormone-stimulated lipolysis is a rapid way to mobilize fat from its storage depotfor use in peripheral tissues. By convention, activation of cytosolic lipases via the β-adrenergic receptor (ADR B2)-cAMP signaling pathway is the only molecular mechanism considered to liberate fatty acids from triglycerides stored in lipid droplets (LDs)of cells. Herein, we provide evidence that, aside from the activation of cytosolic lipases, autophagy contributes to this hormonestimulated lipolysis. The ADR B2-stimulated lipolysis was reduced after inhibition of early or late autophagy using either pharmacological inhibitors or shRN A-mediated autophagic gene knockdown. ADR B2 stimulation has caused a marked increase in the autophagy-targeted LDs for lysosomal degradation, which is dependent on the LD-associated RAB7 as evidenced by the use of both shRN A-mediated RAB7 knockdown and a dominant-negative RAB7 mutant. In addition, RAB7 is involved in unstimulated (basal) lipolysis, and mediates the enhanced basal lipolysis in PLIN 1/perilipin 1 knockdown fat cells. In conclusion, our results showed a contribution of lipophagy to both basal and hormone-stimulated lipolysis and that RAB7 plays a pivotal role in the regulation of this autolysosome-mediated lipid degradation in fat cells. © 2013 Landes Bioscience.