Proteomic Analysis Augments Lipidomic and Metabolomic Understanding of Hepatic Changes on High Fat Diets

摘要

Good differentiation was observed between high fat (HF) and low fat (LF) high carbohydrate diets. Differential and significant pathways by protein analysis agree well with previous small molecule observations including ceramide signaling, glutathione abundance, and carnitine processing and shuttling enzymes. Proteins identified as over-expressed in the HF liver samples show highly significant enrichment of PPAR Signaling Pathway (rno03320 : 1.0E-11; 1.9E-10), the fatty acid degradation pathway (rno00071: 1.9E-13; 7.2E-12), the fatty acid metabolism pathway (rno01212: 3.7E-11; 4.6E-10), and the valine, leucine and isoleucine degradation pathway (2.0E-7; 1.8E-6). The peroxisome pathway observations corroborate our previous metabolomics analyses which showed elevated glutathione levels in the same samples (ref 1), indicative of peroxisomal activity and corresponding elevation of reactive oxygen species (creating endogenous oxidative stress). Among 11 identified proteins from the fatty acid metabolic pathway (of 45 proteins) is the liver isoform of carnitine O-palmitoyltransferase which catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine. This agrees with our previous report showing significant alteration of carnitines and related metabolite levels in HF samples, relative to standard chow.