Proteomic Analysis Of Tissue Proteins And Lipid Droplet Proteins In Mouse Liver After Fasting18Hours

Fasting is an important factor to cause malnutrition metabolic diseases and even death. At the early stage of fasting, despite reduction in liver weight, the anatomical experiments clearly indicates there is a fat liver phenotype. To understand better molecular mechanisms of the early fasting and its physiological and pathological impacts, we used mass spectrometry, a powerful proteomics technology, combined with bioinformatics analysis, to systematically analyze the protein expression changes in the liver and dynamic changes of lipid droplet proteins during the early fasting. We found that mice at fasting18h time-point, serum TG and Leptin level were significantly increased when compared with other early fasting time-point. We identified7151liver proteins and3805lipid droplets proteins (LDP, which are referred to those proteins enriched in the lipid droplets preparation after fasting18h). The functions of top candidates are related to lipid metabolism, molecular transport, and small molecule biochemistry, and some common pathological toxicological conditions such as hepatic necrosis, liver proliferation and liver regeneration. In two independent experiments,221liver proteins were found to up regulated1.5-fold,340proteins down regulated2-fold; and three independent experimental showed that217LDPs increased more than1.5fold and35decreased than2fold, respectively. IPA analysis shows that collection of differentially expressed proteins implicates the increase in PPARα function and decrease in the functions of EHHADH and HSD17B4. FunDO analysis indicates that the changes in both liver proteins and LDP are closely related to diabetes and Alzheimer’s disease; these findings may help the identification of potential biomarkers or therapeutic interventions of these diseases. Upon18h fasting, individual proteins such as St3gal5, Retsat, pPt1, Plin2Eci3, Cyp4al4, Cyp4a10, CPT1A, Cog7, Bdhl were found to increase in liver and LDP, while the level of Pfkp decreased. These proteins can be used as candidate proteins for further analysis of their roles in the control of fasting-induced physiological and pathological responses.