All‐trans retinoic acid promotes fatty acid oxidation in human hepatoma (HepG2) cells (LB612)

Abstract

It has recently emerged that retinoic acid (RA) acts as a ligand for peroxisome proliferator activated receptor (PPAR), a master nuclear receptor of lipid metabolism, in addition to the retinoic acid receptor. The role of all‐trans‐RA (atRA) on regulating lipid metabolism is, however, not clearly understood. In the present study, we examined the effect of atRA on fatty acid oxidation (FAO) in human hepatoma (HepG2) cells. HepG2 cells were cultured in presence or absence of atRA for 24 or 72 hrs, after which, cells were harvested to isolate RNA/protein to check gene/protein expression. Proteomics analysis performed on isolated protein after 72hrs of incubation with atRA showed that atRA significantly increased expression of key enzymes involved in FAO pathway such as acyl CoA dehydrogenase, long chain fatty acyl CoA ligase 3 and 4, delta (3, 5)‐delta (2, 4)‐dienoyl‐CoA isomerase and mitochondrial ATP synthase subunit alpha. Additionally, treatment with atRA significantly increased the mRNA of PPARδ, PPARα and its co‐activator PGC1α, and PPARα/δ target genes: CPT1α, PDK4 and FGF19, which all have role in FAO. Collectively, these results indicate that atRA promotes FAO via PPARα/δ induction in a dose dependent manner. Thus, our findings improve our understanding of RA role in lipid metabolism and signaling in liver.Grant Funding Source: Supported by NIH R01 GM081569 and GM081569‐S1