Conjugated Linoleic Acid (CLA) and Alpha Linolenic Acid (ALA) Improve Cholesterol Homeostasis in Obesity by Modulating Distinct Hepatic Protein Pathways.

High fat diet (HFD)-induced obesity impairs macrophage-to-feces reverse cholesterol transport (RCT). We hypothesized that dietary supplementation with the polyunsaturated fatty acids (PUFA) conjugated linoleic acid (CLA) or alpha linolenic acid (ALA) would prevent HFD-impaired RCT by modulating hepatic protein pathways.

ApoE3L.CETP mice were fed a HFD supplemented ± CLA or ALA for 12 weeks and in vivo macrophage-to-feces RCT was determined. Hepatic cholesterol transporters and the hepatic proteome were assessed by immunoblotting and mass spectrometry respectively. Mice fed HFD alone, but not ALA-HFD or CLA-HFD, exhibited increased systemic cholesterol levels, increased ³ H-cholesterol levels in plasma and liver but not feces during RCT, and reduced hepatic ABCG5/8 expression relative to LFD. ALA-HFD significantly reduced liver weight, hepatic cholesterol levels and expression of the cholesterol synthesis enzyme farnesyl pyrophosphate synthase (FDPS) relative to HFD. ALA further increased expression of acetyl-coA oxidase (Acox1)-associated proteins and suppressed PPARα-induced proteins relative to HFD. CLA did not significantly attenuate hepatic lipid levels but was associated with reduced hepatic expression of fatty acid binding protein (FABP)-1/FABP4 levels relative to HFD, and reduced inflammatory pathway activation relative to ALA-HFD.

ALA and CLA exert distinct mechanistic advantages on cholesterol homeostasis and RCT in obesity. This article is protected by copyright. All rights reserved.