title: t10,c12 conjugated linoleic acid upregulates hepatic de novo lipogenesis and triglyceride synthesis via mTOR pathway activation.
abstract: In mice, supplementation of t10,c12 conjugated linoleic acid (CLA) increases liver mass and hepatic steatosis via increasing uptake of fatty acids released from adipose tissues. However, the effects of t10,c12 CLA on hepatic lipid synthesis and the associated mechanisms are largely unknown. Thus, we tested the hypothesis that gut microbiota-producing t10,c12 CLA would induce de novo lipogenesis and triglyceride (TG) synthesis in HepG2 cells, promoting lipid accumulation. It was found that treatment with t10,c12 CLA (100 micrometer) for 72 h increased neutral lipid accumulation via enhanced incorporation of acetate, palmitate, oleate, and 2- deoxyglucose into TG. Furthermore, treatment with t10,c12 CLA led to increased mRNA expression and protein levels of lipogenic genes including SREBP1, ACC1, FASN, ELOVL6, GPAT1, and DGAT1, presenting potential mechanisms by which CLA may increase lipid deposition. Most strikingly, t10,c12 CLA treatment for 3 h increased phosphorylation of mTOR, S6K, and S6. Taken together, gut microbiota-producing t10,c12 CLA activates hepatic de novo lipogenesis and TG synthesis through activation of the mTOR/SREBP1 pathway, with consequent lipid accumulation in HepG2 cells.
authors.affiliation: BK 21 Plus Graduate Program, Department of Animal Science and Institute of Rare Earth for Biological Application, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors.forename: Gwang-woong
authors.initials: GW
authors.lastname: Go
authors.forename: Sangnam
authors.initials: S
authors.lastname: Oh
authors.forename: Miri
authors.initials: M
authors.lastname: Park
authors.forename: Gyoungok
authors.initials: G
authors.lastname: Gang
authors.forename: Danielle
authors.initials: D
authors.lastname: McLean
authors.forename: Han-sul
authors.initials: HS
authors.lastname: Yang
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Song
authors.forename: Younghoon
authors.initials: Y
authors.lastname: Kim
mesh_terms: D001419:Bacteria / Q000378:metabolism; D020869:Gene Expression Profiling; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000378:metabolism*; D050155:Lipogenesis / Q000187:drug effects*; D053858:Metabolic Networks and Pathways; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014280:Triglycerides / Q000096:biosynthesis*
chemical_list: D044243:Linoleic Acids, Conjugated; D014280:Triglycerides; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases