Journal of Liver

Proteomics studies of the impact of high fat diet on proteome of mouse liver and dual mode of pharmacological action of Mangiferin

World Congress on Hepatitis

July 20-22, 2015 Orlando, Florida, USA

Yuling Chi

Posters-Accepted Abstracts: J Liver

Abstract:

Chronic over-nutrition is a major contributor to the rapidly growing incidence of obesity and its related metabolic disorders such as nonalcoholic fatty liver disease (NAFLD). The molecular mechanisms of metabolic dysregulation leading to these pathological conditions remain unclear, thus no effective therapy is currently available.We have identified a natural compound, mangiferin (MGF) (a predominant component of the plants of Anemarrhena asphodeloides and Mangifera indica), that can protect against high fat diet (HFD) induced obesity, hyperglycemia, insulin resistance and hyperlipidemia in mice. To understand MGF molecular mechanisms of action, we developed stable isotope labeling of mammalian (SILAM) technology and performed unbiased quantitative proteomic analysis of protein profiles in liver of mice fed with chow diet (CD) and HFD with or without MGF treatment, utilizing 15N metabolically labeled liver proteins as internal standards. We detected and quantitatively compared 965 proteins between CD and HFD groups and 865 proteins between HFD and HFD + MGF. We found that HFD significantly altered 192 proteins and MGF significantly differentially regulated 87 proteins. Among all significantly altered proteins 50% are involved in metabolic processes, which are further classified into 8 - 9 metabolic processes. The majority of HFD modulated proteins participate in lipid metabolism. HFD induced proteins involved in fatty acid uptake and subsequent oxidation and suppressed lipid biosynthesisrelated proteins. Impressively, MGF was able to differentially regulate proteins that are altered by HFD. MGF up-regulates proteins pivotal for mitochondrial bioenergetics which are networked to PPAR? and PGC-1?, and down-regulates proteins that control de novo lipogenesis and networked to SREBP and PPAR?. This novel mode of dual pharmacodynamic actions enables MGF to enhance energy expenditure and inhibit lipogenesis, and thereby correct HFD induced liver steatosis and prevent adiposity. This provides a molecular basis supporting development of MGF or its derivatives into therapeutics to treat metabolic disorders.