Elaidic acid increases hepatic lipogenesis by mediating sterol regulatory element binding protein-1c activity in HuH-7 cells.
The liver is the major organ responsible for lipid biosynthesis. Sterol regulatory element-binding proteins (SREBP) are major transcription factors that regulate the expression of genes regulating fatty acid and cholesterol biosynthesis. Here we show that elaidic acid upregulates hepatic de-novo fatty acid and cholesterol synthesis in HuH-7 cells. To define the molecular mechanism involved in this unique regulation on hepatic lipogenesis, luciferase reporter gene assays were performed in HEK293 cells to compare the regulation of sterol regulatory element (SRE) that is present in SREBP-target promoter by elaidic acid and oleic acid. The results show that elaidic acid potently induced SRE-luciferase activity, whereas oleic acid inhibited this activity. Furthermore, elaidic acid increased SREBP-1c mRNA, while oleic acid did not alter it. Oleic acid inhibited mature form of SREBP-1 protein level, while elaidic acid did not show inhibitory effects. In addition, elaidic acid was also found to increase several selected lipogenic genes that are involved in fatty acids and sterol synthesis. These data demonstrate a unique role of elaidic acid, the most abundant trans fatty acid, in modulating hepatic lipogenesis.
Edward A. Doisy Department of Biochemistry and Molecular Biology, Center for Cardiovascular Research, Saint Louis University School of Medicine, St. Louis, MO, 63104, USA.
Fei
F
Shao
David A
DA
Ford
D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000096:biosynthesis; D005227:Fatty Acids / Q000096:biosynthesis; D057809:HEK293 Cells; D006801:Humans; D050155:Lipogenesis / Q000187:drug effects*; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D019301:Oleic Acid / Q000494:pharmacology*; D009829:Oleic Acids; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
D005227:Fatty Acids; D009829:Oleic Acids; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D019301:Oleic Acid; C011459:elaidic acid; D002784:Cholesterol