Therapeutic hexapeptide (PGPIPN) prevents and cures alcoholic fatty liver disease by affecting the expressions of genes related with lipid metabolism and oxidative stress

// Nan Qi 1, * , Chen Liu 1, 2, * , Haoran Yang 1, 3, * , Wanrong Shi 4 , Shenyi Wang 1 , Yan Zhou 1 , Cai Wei 5 , Fang Gu 1 and Yide Qin 1 1 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, China 2 Clinical Laboratory, Guangming Center Hospital, Shenzhen, Guangdong 518107, China 3 Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China 4 Department of Internal Medicine, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China 5 Department of Pharmacy, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, China * These authors have contributed equally to this work Correspondence to: Yide Qin, email: yideqin@ahmu.edu.cn Keywords: PGPIPN, alcoholic fatty liver, steatosis, gene expression Received: June 21, 2017     Accepted: August 28, 2017     Published: September 30, 2017 ABSTRACT PGPIPN is a therapeutic hexapeptide derived from bovine β-casein. Here we investigated the role and mechanism of this peptide on alcoholic fatty liver disease (AFLD). We took human hepatic cell line LO2 and hepatocellular carcinoma cell line HepG2 to establish the models of steatosis hepatocyte induced by alcohol, taken PGPIPN as pharmacological intervention. And we also established the model of AFLD mice, taken PGPIPN as therapeutic drug and glutathione (GSH) as positive control. We assayed the biochemical materials related to liver injury, lipid metabolism and oxidation, and observed morphology change and fat accumulation of hepatocyte. The gene expressions and/or activities related to liver injury, lipid metabolism and oxidation, such as ACC, PPAR-γ, CHOP and Caspase-3, were assessed by real time PCR and western blot. Our results showed PGPIPN alleviated hepatic steatosis in both model cells and AFLD model mice. PGPIPN can effectively reduce the lipid accumulation and oxidative stress of hepatocyte in a dose-dependent manner. PGPIPN alleviated alcohol-induced cell steatosis and injuries by regulating the gene expressions and/or activities of ACC, PPAR-γ, CHOP and Caspase-3. Our results demonstrated PGPIPN had the protective and therapeutic effect on AFLD, which may serve as a potential therapeutic agent for AFLD.