title: Impact of high-fat diet on the proteome of mouse liver.
abstract: Chronic overnutrition, for instance, high-fat diet (HFD) feeding, is a major cause of rapidly growing incidence of metabolic syndromes. However, the mechanisms underlying HFD-induced adverse effects on human health are not clearly understood. HFD-fed C57BL6/J mouse has been a popular model employed to investigate the mechanisms. Yet, there is no systematic and comprehensive study of the impact of HFD on the protein profiles of the animal. Here, we present a proteome-wide study of the consequences of long-term HFD feeding. Utilizing a powerful technology, stable isotope labeling of mammals, we detected and quantitatively compared 965 proteins extracted from livers of chow-diet-fed and HFD-fed mice. Among which, 122 proteins were significantly modulated by HFD. Fifty-four percent of those 122 proteins are involved in metabolic processes and the majority participate in lipid metabolism. HFD up-regulates proteins that play important roles in fatty acid uptake and subsequent oxidation and are linked to the transcription factors PPARα and PGC-1α. HFD suppresses lipid biosynthesis-related proteins that play major roles in de novo lipogenesis and are linked to SREBP-1 and PPARγ. These data suggest that HFD-fed mice tend to develop enhanced fat utilization and suppressed lipid biosynthesis, understandably a self-protective mechanism to counteract to excessive fat loading, which causes liver steatosis. Enhanced fatty acid oxidation increases reactive oxygen species and inhibits glucose oxidation, which are associated with hyperglycemia and insulin resistance. This proteomics study provides molecular understanding of HFD-induced pathology and identifies potential targets for development of therapeutics for metabolic syndromes.
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, USA.
authors.forename: Outhiriaradjou
authors.initials: O
authors.lastname: Benard
authors.affiliation: The Laboratory for Macromolecular Analysis and Proteomics, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, USA; Department of Pathology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, USA.
authors.forename: Jihyeon
authors.initials: J
authors.lastname: Lim
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, USA.
authors.forename: Pasha
authors.initials: P
authors.lastname: Apontes
authors.affiliation: Computational Biology Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Jing
authors.affiliation: The Laboratory for Macromolecular Analysis and Proteomics, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, USA.
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Angeletti
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, USA. Electronic address: yuling.chi@einstein.yu.edu.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Chi
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D005234:Fatty Liver / Q000209:etiology; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology; D020543:Proteome / Q000378:metabolism*
chemical_list: D020543:Proteome
keywords: High fat diet; Lipid metabolism; Mouse; Nutrition; Proteomics