title: Trans-10, cis-12 conjugated linoleic acid inhibits prolactin-induced cytosolic NADP+ -dependent isocitrate dehydrogenase expression in bovine mammary epithelial cells.
abstract: Conjugated linoleic acid (CLA) has been found to exert beneficial effects on lipid profile and repress de novo fatty acid synthesis in mammary gland during lactation. However, the underlying mechanisms responsible for the antilipogenic effects of CLA have not been established. The cytosolic NADP+ -dependent isocitrate dehydrogenase (IDH1) plays a critical role in cholesterol and fatty acid biosynthesis by providing reducing equivalents as NADPH. In previous studies, we documented that the expression of IDH1 in bovine mammary epithelium was modulated by regulators of mammary differentiation and metabolic effectors. In this study, we investigated the short-term effects of prolactin (PRL) and CLA on IDH1 expression in BME-UV bovine mammary epithelial cells. In time-course experiments, we found that the treatment with PRL for 60 and 90 min elicited a significant increase in IDH1 transcript levels. Conversely, the cotreatment of BME-UV cells with PRL plus a CLA mixture for 90 min prevented the accumulation of IDH1 mRNA induced by PRL. In addition, we found that the trans-10, cis-12 CLA, but not the cis-9, trans-11 CLA isomer, inhibited basal- and PRL-induced IDH1 mRNA expression. The inhibitory effects of the trans-10, cis-12 CLA isomer on PRL-induced IDH1 expression accumulation were confirmed by quantitative real time PCR and western-blotting analysis. We propose that the inhibitory effects of CLA on milk fat synthesis in mammary epithelial cells may derive, at least in part, from repression of IDH1 expression.
authors.affiliation: Laboratory of Mammary Gland Biology, Department of Nutritional Sciences, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Liu
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Degner
authors.forename: Donato F
authors.initials: DF
authors.lastname: Romagnolo
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003600:Cytosol / Q000201:enzymology*; D004847:Epithelial Cells / Q000201:enzymology; D064429:Fatty Acid Synthases / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008321:Mammary Glands, Animal / Q000201:enzymology*; D011388:Prolactin / Q000037:antagonists & inhibitors*; D011494:Protein Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D044243:Linoleic Acids, Conjugated; D012333:RNA, Messenger; D011388:Prolactin; D007521:Isocitrate Dehydrogenase; C039355:isocitrate dehydrogenase (NADP+); D064429:Fatty Acid Synthases; D011494:Protein Kinases; C033288:(acetyl-CoA carboxylase) kinase