Fig. 8
From: Adiponectin triggers breast cancer cell death via fatty acid metabolic reprogramming
Proposed model for the modulation of tumor fatty acid metabolism by adiponectin. Adiponectin has been reported to potently suppress breast cancer growth. This study focuses on effects of adiponectin on tumor fatty acid metabolism and provides a novel mechanism for its breast cancer suppressing activity. SIRT-1 plays a central role in metabolic actions of adiponectin in breast cancer cells. On the one hand, SIRT-1 induction leads to downregulation of SREBP-1 by direct deacetylation and destabilization of nuclear SREBP-1 or by suppressing SREBP-1 expression through inhibition of mTOR signaling. SREBP-1 suppression leads to decreased expression of key enzymes in fatty acid synthesis (FAS) pathway and resultant blockage of FAS. On the other, SIRT-1 induction by adiponectin stimulates lipophagy to degrade lipid droplets and promote utilization of fatty acids for energy production via fatty acid oxidation (FAO). Inhibition of FAS accompanied by elevated FAO result in impairment in cellular fatty acid pool, which in turn causes disruption of lipid rafts and raft-dependent signal transduction, and cell apoptosis as a final consequence