title: ChREBP and LXRα mediate synergistically lipogenesis induced by glucose in porcine adipocytes.
abstract: Glucose is a substrate for fatty acid synthesis, and induces lipogenesis and expressions of lipogenic genes. It was proposed that transcriptional factor ChREBP, LXRα and SREBP-1c are key mediators in lipogenesis induced by glucose, however the underlying mechanism remains unclear in porcine adipocytes. In this study, glucose stimulated lipogenesis and expressions of ChREBP, LXRα, SREBP-1c and lipogenic genes FAS and ACC1 in primary porcine adipocytes. When ChREBP expression was knocked down by RNAi, lipogenesis and FAS and ACC1 expressions decreased significantly, and lipogenesis induced by glucose decreased by 75.6%, whereas neither the basal expressions under glucose-free nor glucose induced expressions of LXRα and SREBP-1c were evidently affected, suggesting that ChREBP was a main mediator of lipogenesis stimulated by glucose. Glucose promoted LXRα gene expression, and activation of LXRα by T0901317 increased SREBP-1c expression and enhanced the stimulation of glucose on lipogenesis, but this stimulatory effect of LXRα depended on glucose. Activated LXRα stimulated lipogenesis and ChREBP mRNA expression, which was much lower than that elevated by glucose, and was markedly lower in ChREBP-silencing than in unperturbed adipocytes. SREBP-1c activation blocked by fatostatin markedly decreased lipogenesis and expressions of FAS and ACC1 induced by glucose. Lipogenesis and lipogenic gene expression stimulated by LXRα activation were attenuated by fatostatin, however there was still a slightly increase in ChREBP-silencing adipocytes. These dates suggested that LXRα could directly or through SREBP-1c mediate the lipogenesis induced by glucose. Together, glucose induced lipogenesis and lipogenic gene expressions directly through ChREBP, and directly through LXRα or via SREBP-1c.
authors.affiliation: College of Life Science and Engineering, Northwest University for Nationalities, Lanzhou, Gansu 730030, China.
authors.forename: Guo Hua
authors.initials: GH
authors.lastname: Zhang
authors.affiliation: College of Life Science and Engineering, Northwest University for Nationalities, Lanzhou, Gansu 730030, China. Electronic address: smljx@xbmu.edu.cn.
authors.forename: Jian Xiong
authors.initials: JX
authors.lastname: Lu
authors.affiliation: College of Life Science and Engineering, Northwest University for Nationalities, Lanzhou, Gansu 730030, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: College of Life Science and Engineering, Northwest University for Nationalities, Lanzhou, Gansu 730030, China.
authors.forename: Peng Hui
authors.initials: PH
authors.lastname: Guo
authors.affiliation: Gansu Engineering Research Center for Animal Cell, Northwest University for Nationalities, Lanzhou, Gansu 730030, China.
authors.forename: Zi Lin
authors.initials: ZL
authors.lastname: Qiao
authors.affiliation: Gansu Engineering Research Center for Animal Cell, Northwest University for Nationalities, Lanzhou, Gansu 730030, China.
authors.forename: Ruo Fei
authors.initials: RF
authors.lastname: Feng
authors.affiliation: College of Life Science and Engineering, Northwest University for Nationalities, Lanzhou, Gansu 730030, China.
authors.forename: Shi En
authors.initials: SE
authors.lastname: Chen
authors.affiliation: Gansu Engineering Research Center for Animal Cell, Northwest University for Nationalities, Lanzhou, Gansu 730030, China.
authors.forename: Jia Lin
authors.initials: JL
authors.lastname: Bai
authors.affiliation: College of Life Science and Engineering, Northwest University for Nationalities, Lanzhou, Gansu 730030, China.
authors.forename: Sheng Dong
authors.initials: SD
authors.lastname: Huo
authors.affiliation: Gansu Engineering Research Center for Animal Cell, Northwest University for Nationalities, Lanzhou, Gansu 730030, China. Electronic address: mzr@xbmu.edu.cn.
authors.forename: Zhong Ren
authors.initials: ZR
authors.lastname: Ma
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D050155:Lipogenesis / Q000187:drug effects*; D000071518:Liver X Receptors; D008297:Male; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D034421:Sus scrofa; D013844:Thiazoles / Q000494:pharmacology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D005947:Glucose; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D011725:Pyridines; D034741:RNA, Small Interfering; D013449:Sulfonamides; D013844:Thiazoles; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C545733:fatostatin
keywords: ChREBP; Glucose; LXRα; Lipogenesis; Primary porcine adipocyte