Peroxisome proliferator-activated receptor activation favours selective subcutaneous lipid deposition by coordinately regulating lipoprotein lipase modulators, fatty acid transporters and lipogenic enzymes

AimPeroxisome proliferator-activated receptor (PPAR) activation is associated with preferential lipoprotein lipase (LPL)-mediated fatty acid storage in peripheral subcutaneous fat depots. How PPAR agonism acts upon the multi-level modulation of depot-specific lipid storage remains incompletely understood. MethodsWe evaluated herein triglyceride-derived lipid incorporation into adipose tissue depots, LPL mass and activity, mRNA levels and content of proteins involved in the modulation of LPL activity and fatty acid transport, and the expression/activity of enzymes defining adipose tissue lipogenic potential in rats treated with the PPAR ligand rosiglitazone (30mgkg(-1)day(-1), 23days) after either a 10-h fasting period or a 17-h fast followed by 6h of adlibitum refeeding. ResultsRosiglitazone stimulated lipid accretion in subcutaneous fat (SF) similar to twofold and significantly reduced that of visceral fat (VF) to nearly half. PPAR activation selectively increased LPL mass, activity and the expression of its chaperone LMF1 in SF. In VF, rosiglitazone had no effect on LPL activity and downregulated the mRNA levels of the transendothelial transporter GPIHBP1. Overexpression of lipid uptake and fatty acid transport proteins (FAT/CD36, FATP1 and FABP4) and stimulation of lipogenic enzyme activities (GPAT, AGPAT and DGAT) upon rosiglitazone treatment were of higher magnitude in SF. ConclusionsTogether these findings demonstrate that the depot-specific transcriptional control of LPL induced by PPAR activation extends to its key interacting proteins and post-translational modulators to favour subcutaneous lipid storage.