title: Trans-10, cis-12 conjugated linoleic acid decreases de novo lipid synthesis in human adipocytes.
abstract: Conjugated linoleic acid (CLA) reduces adiposity in vivo. However, mechanisms mediating these changes are unclear. Therefore, we treated cultures of human adipocytes with trans-10, cis-12 (10,12) CLA, cis-9, trans-11 (9,11) CLA or other trans fatty acids (FA), and measured indices of lipid metabolism. The lipid-lowering effects of 10,12 CLA were unique, as other trans FA did not reduce TG content to the same extent. Using low levels of [(14)C]-CLA isomers, it was shown that both isomers were readily incorporated into acylglycerols and phospholipids, albeit at lower levels than [(14)C]-oleic or [(14)C]-linoleic acids. When using [(14)C]-acetic acid and [(14)C]-pyruvic acid as substrates, 30 μM 10,12 CLA, but not 9,11 CLA, decreased de novo synthesis of triglyceride, free FA, diacylglycerol, cholesterol esters, cardiolipin, phospholipids and ceramides within 3-24 h. Treatment with 30 μM 10,12 CLA, but not 9,11 CLA, decreased total cellular lipids within 3 days and the ratio of monounsaturated FA (MUFA) to saturated FA, and increased C18:0 acyl-CoA levels within 24 h. Consistent with these data, stearoyl-CoA desaturase (SCD)-1 mRNA and protein levels were down-regulated by 10,12 CLA within 7-12 h, respectively. The mRNA levels of liver X receptor (LXR)α and sterol regulatory element binding protein (SREBP)-1c, transcription factors that regulate SCD-1, were decreased by 10,12 CLA within 5 h. These data suggest that the isomer-specific decrease in de novo lipid synthesis by 10,12 CLA is due, in part, to the rapid repression of lipogenic transcription factors that regulate MUFA synthesis, suggesting an anti-obesity mechanism unique to this trans FA.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Obsen
authors.forename: Nils J
authors.initials: NJ
authors.lastname: Faergeman
authors.forename: Soonkyu
authors.initials: S
authors.lastname: Chung
authors.forename: Kristina
authors.initials: K
authors.lastname: Martinez
authors.forename: Semone
authors.initials: S
authors.lastname: Gobern
authors.forename: Olivier
authors.initials: O
authors.lastname: Loreau
authors.forename: Martin
authors.initials: M
authors.lastname: Wabitsch
authors.forename: Susanne
authors.initials: S
authors.lastname: Mandrup
authors.forename: Michael
authors.initials: M
authors.lastname: McIntosh
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000328:Adult; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism; D005260:Female; D006801:Humans; D007536:Isomerism; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects*; D000071518:Liver X Receptors; D008875:Middle Aged; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D044242:Trans Fatty Acids / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D044243:Linoleic Acids, Conjugated; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D044242:Trans Fatty Acids; D014157:Transcription Factors; D014280:Triglycerides; C523776:SCD1 protein, human; D013230:Stearoyl-CoA Desaturase