title: Short communication: effect of trans-10,cis-12 conjugated linoleic acid on activation of lipogenic transcription factors in bovine mammary epithelial cells.
abstract: The objective of this study was to examine the effect of trans-10,cis-12 conjugated linoleic acid (t10c12CLA) on the activation of transcription factors that potentially regulate lipid synthesis in a bovine mammary epithelial cell line (MAC-T). Cells were transfected with luciferase reporter constructs containing sterol response element (SRE and SRE complex) for sterol regulatory element binding protein-1, peroxisome proliferator response element for peroxisome proliferator-activated receptor γ, or liver X receptor response element for liver X receptor. Different concentrations of t10c12CLA (0, 25, 50, 75, or 100μM) were applied to cells to determine the activation of transcription factors. The influence of t10c12CLA bond structure on transcription factor activation was also investigated by treating cells with different 18:1 fatty acid isomers (trans-10 18:1 or cis-12 18:1) at 100μM. Cells were harvested for luciferase assay after 24h of treatment. Compared with linoleic acid and cis-9,trans-11 CLA controls, the SRE reporters had significantly lower activity in t10c12CLA-treated cells at 50 and 75μM for SRE complex and SRE, respectively. Lower SRE and SRE complex activation was observed in t10c12CLA treatment at 25, 50, and 75μM compared with 0μM. The peroxisome proliferator response element and liver X receptor response element reporters did not respond differently between the t10c12CLA treatment and controls. Compared with t10c12CLA, both trans-10 18:1 and cis-12 18:1 increased the activities of SRE and SRE complex reporters by 1.3- to 4.2-fold. In conclusion, t10c12CLA has an inhibitory role in lipogenic transcription factor activation of SRE, and this negative effect is due to the conjugation of trans-10 and cis-12 double bonds in the fatty acid. Furthermore, we found no support for a regulatory role of response elements for peroxisome proliferator-activated receptor γ or liver X receptor in the t10c12CLA inhibition of mammary lipid synthesis.
authors.affiliation: Department of Dairy Science, Virginia Tech, Blacksburg 24061.
authors.forename: L
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Dairy Science, Virginia Tech, Blacksburg 24061.
authors.forename: A J
authors.initials: AJ
authors.lastname: Lengi
authors.affiliation: Department of Dairy Science, Virginia Tech, Blacksburg 24061.
authors.forename: M L
authors.initials: ML
authors.lastname: McGilliard
authors.affiliation: Department of Animal Science, Cornell University, Ithaca, NY 14853.
authors.forename: D E
authors.initials: DE
authors.lastname: Bauman
authors.affiliation: Department of Dairy Science, Virginia Tech, Blacksburg 24061. Electronic address: bcorl@vt.edu.
authors.forename: B A
authors.initials: BA
authors.lastname: Corl
mesh_terms: D000818:Animals; D002417:Cattle; D002452:Cell Count; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D007536:Isomerism; D019787:Linoleic Acid; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D050155:Lipogenesis; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D044243:Linoleic Acids, Conjugated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D019787:Linoleic Acid
keywords: luciferase reporter; trans-10,cis-12 conjugated linoleic acid; transcription factor