title: Docosahexaenoic Acid Ameliorates Fructose-Induced Hepatic Steatosis Involving ER Stress Response in Primary Mouse Hepatocytes.
abstract: The increase in fructose consumption is considered to be a risk factor for developing nonalcoholic fatty liver disease (NAFLD). We investigated the effects of docosahexaenoic acid (DHA) on hepatic lipid metabolism in fructose-treated primary mouse hepatocytes, and the changes of Endoplasmic reticulum (ER) stress pathways in response to DHA treatment. The hepatocytes were treated with fructose, DHA, fructose plus DHA, tunicamycin (TM) or fructose plus 4-phenylbutyric acid (PBA) for 24 h. Intracellular triglyceride (TG) accumulation was assessed by Oil Red O staining. The mRNA expression levels and protein levels related to lipid metabolism and ER stress response were determined by real-time PCR and Western blot. Fructose treatment led to obvious TG accumulation in primary hepatocytes through increasing expression of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC), two key enzymes in hepatic de novo lipogenesis. DHA ameliorates fructose-induced TG accumulation by upregulating the expression of carnitine palmitoyltransferase 1A (CPT-1α) and acyl-CoA oxidase 1 (ACOX1). DHA treatment or pretreatment with the ER stress inhibitor PBA significantly decreased TG accumulation and reduced the expression of glucose-regulated protein 78 (GRP78), total inositol-requiring kinase 1 (IRE1α) and p-IRE1α. The present results suggest that DHA protects against high fructose-induced hepatocellular lipid accumulation. The current findings also suggest that alleviating the ER stress response seems to play a role in the prevention of fructose-induced hepatic steatosis by DHA.
authors.affiliation: School of Public Health and Management, Chongqing Medical University, Research Center for Medicine and Social Development, Innovation Center for Social Risk Governance in Health, Chongqing 400016, China. jinyingzheng1988@163.com.
authors.forename: Jinying
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Laboratory of Lipid &amp; Glucose Metabolism, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. 13527441813@163.com.
authors.forename: Chuan
authors.initials: C
authors.lastname: Peng
authors.affiliation: School of Public Health and Management, Chongqing Medical University, Research Center for Medicine and Social Development, Innovation Center for Social Risk Governance in Health, Chongqing 400016, China. aiyanbiao1992@163.com.
authors.forename: Yanbiao
authors.initials: Y
authors.lastname: Ai
authors.affiliation: Laboratory of Lipid &amp; Glucose Metabolism, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. hengyy663@163.com.
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Laboratory of Lipid &amp; Glucose Metabolism, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. xiaoxq@cqmu.edu.cn.
authors.forename: Xiaoqiu
authors.initials: X
authors.lastname: Xiao
authors.affiliation: School of Public Health and Management, Chongqing Medical University, Research Center for Medicine and Social Development, Innovation Center for Social Risk Governance in Health, Chongqing 400016, China. ljb21st@126.com.
authors.forename: Jibin
authors.initials: J
authors.lastname: Li
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D064429:Fatty Acid Synthases / Q000378:metabolism; D005234:Fatty Liver / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D005632:Fructose; D006360:Heat-Shock Proteins / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects*; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000201:enzymology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D010654:Phenylbutyrates; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013312:Stress, Physiological; D014280:Triglycerides / Q000378:metabolism; D014415:Tunicamycin; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D008565:Membrane Proteins; D010654:Phenylbutyrates; D014280:Triglycerides; D014415:Tunicamycin; D004281:Docosahexaenoic Acids; D005632:Fructose; C075773:4-phenylbutyric acid; D002334:Carnitine O-Palmitoyltransferase; D064429:Fatty Acid Synthases; C486556:Ern2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D000103:Acetyl-CoA Carboxylase
keywords: ER stress; NAFLD; docosahexaenoic acid; fructose