Roles of Peroxisome Proliferator-Activated Receptor α in Bitter Melon Seed Oil-Corrected Lipid Disorders and Conversion of α-Eleostearic Acid into Rumenic Acid in C57BL/ 6J Mice

We previously reported that bitter melon seed oil (BMSO) was an effective anti-steatosis and antiobesity agent. Since the major fatty acid alpha-eleostearic acid (alpha-ESA) in BMSO is a peroxisome proliferator-activated receptor alpha (PPAR alpha) activator, the objective was to investigate the role of PPAR alpha in BMSO-modulated lipid disorders and alpha-ESA metabolism. C57BL/ 6J wild (WD) and PPAR alpha knockout (KO) mice were fed a high-fat diet containing BMSO (15% soybean oil + 15% BMSO, HB) or not (30% soybean oil, HS) for 5 weeks. The HB diet significantly reduced hepatic triglyceride concentrations and increased acyl-CoA oxidase activity in WD, but not in KO mice. However, regardless of genotype, body fat percentage was lowered along with upregulated protein levels of uncoupling protein 1 (UCP1) and tyrosine hydroxylase, as well as signaling pathway of cAMP-dependent protein kinase and AMP-activated protein kinase in the white adipose tissue of HB-treated groups compared to HS cohorts. In WD-HB and KO-HB groups, white adipose tissue had autophagy, apoptosis, inflammation, and browning characteristics. Without PPAR alpha, in vivo reduction of alpha-ESA into rumenic acid was slightly but significantly lowered, along with remarkable reduction of hepatic retinol saturase (RetSat) expression. We concluded that BMSO-mediated anti-steatosis depended on PPAR alpha, whereas the anti-adiposity effect was PPAR ff -independent. In addition, PPAR alpha-dependent enzymes may participate in alpha-ESA conversion, but only have a minor role.