title: Conjugated linoleic acid-induced milk fat depression in lactating ewes is accompanied by reduced expression of mammary genes involved in lipid synthesis.
abstract: Conjugated linoleic acids (CLA) are produced during rumen biohydrogenation and exert a range of biological effects. The trans-10,cis-12 CLA isomer is a potent inhibitor of milk fat synthesis in lactating dairy cows and some aspects of the mechanism have been established. Conjugated linoleic acid-induced milk fat depression has also been observed in small ruminants and our objective was to examine the molecular mechanism in lactating ewes. Multiparous lactating ewes were fed a basal ration (0.55:0.45 concentrate-to-forage ratio; dry matter basis) and randomly allocated to 2 dietary CLA levels (n=8 ewes/treatment). Treatments were zero CLA (control) or 15 g/d of lipid-encapsulated CLA supplement containing cis-9,trans-11 and trans-10,cis-12 CLA isomers in equal proportions. Treatments were fed for 10 wk and the CLA supplement provided 1.5 g of trans-10,cis-12/d. No treatment effects were observed on milk yield or milk composition for protein or lactose at wk 10 of the study. In contrast, CLA treatment significantly decreased both milk fat percentage and milk fat yield (g/d) by about 23%. The de novo synthesized fatty acids (FA; <C16) were significantly decreased in proportion (15%) and daily yield (27%), and the proportion of preformed FA (>C16) was increased (10%) for the CLA treatment. In agreement with the reduced de novo FA synthesis, mRNA abundance of acetyl-coenzyme A carboxylase α, FA synthase, stearoyl-CoA desaturase 1, and glycerol-3-phosphate acyltransferase 6 decreased by 25 to 40% in the CLA-treated group. Conjugated linoleic acid treatment did not significantly reduce the mRNA abundance of enzymes involved in NADPH production, but the mRNA abundance for sterol regulatory element-binding factor 1 and insulin-induced gene 1, genes involved in regulation of transcription of lipogenic enzymes, was decreased by almost 30 and 55%, respectively, with CLA treatment. Furthermore, mRNA abundance of lipoprotein lipase decreased by almost 40% due to CLA treatment. In conclusion, the mechanism for CLA-induced milk fat depression in lactating ewes involved the sterol regulatory element-binding protein transcription factor family and a coordinated downregulation in transcript abundance for lipogenic enzymes involved in mammary lipid synthesis.
authors.affiliation: Department of Animal Science, Cornell University, Ithaca, NY 14853, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hussein
authors.forename: K H
authors.initials: KH
authors.lastname: Harvatine
authors.forename: W M P B
authors.initials: WM
authors.lastname: Weerasinghe
authors.forename: L A
authors.initials: LA
authors.lastname: Sinclair
authors.forename: D E
authors.initials: DE
authors.lastname: Bauman
mesh_terms: D000818:Animals; D004032:Diet / Q000662:veterinary; D005223:Fats / Q000032:analysis*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007774:Lactation; D044243:Linoleic Acids, Conjugated / Q000008:administration & dosage / Q000494:pharmacology*; D008055:Lipids / Q000096:biosynthesis; D050155:Lipogenesis / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000235:genetics; D008321:Mammary Glands, Animal / Q000378:metabolism*; D008892:Milk / Q000737:chemistry*; D008894:Milk Proteins / Q000032:analysis; D016133:Polymerase Chain Reaction / Q000662:veterinary; D011897:Random Allocation; D012756:Sheep / Q000502:physiology*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics
chemical_list: D005223:Fats; D044243:Linoleic Acids, Conjugated; D008055:Lipids; D008894:Milk Proteins; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D008071:Lipoprotein Lipase