title: Effects of short- and long-chain fatty acids on the expression of stearoyl-CoA desaturase and other lipogenic genes in bovine mammary epithelial cells.
abstract: Stearoyl-CoA desaturase (SCD) in the bovine mammary gland introduces a cis-double bond at the Δ9 position in a wide range of fatty acids (FA). Several long-chain polyunsaturated fatty acids (PUFA) inhibit expression of SCD, but information on the effect of short-chain fatty acids on mammary SCD expression is scarce. We used a bovine mammary cell line (MAC-T) to assess the effect of acetic acid (Ac) and β-hydroxybutyric acid (BHBA) in comparison with the effect of various long-chain fatty acids on the mRNA expression of the lipogenic enzymes SCD, acetyl-CoA carboxylase (ACACA), fatty acid synthase (FASN) and their associated gene regulatory proteins sterol regulatory element binding transcription factor 1 (SREBF1), insulin-induced gene 1 protein (INSIG1) and peroxisome proliferator-activated receptor alpha (PPARA)and peroxisome proliferator-activated receptor delta (PPARD) by quantitative real-time PCR. MAC-T cells were treated for 12 h without FA additions (CON) or with either 5 mM Ac, 5 mM BHBA, a combination of 5 mM Ac + 5 mM BHBA, 100 μM C16:0, 100 μM C18:0, 100 μM C18:1 cis-9, 100 μM C18:1 trans-11, 100 μM C18:2 cis-9,12 or 100 μM C18:3 cis-9,12,15. Compared with control, mRNA expression of SCD1 was increased by Ac (+61%) and reduced by C18:1 cis-9 (-61%), C18:2 cis-9,12 (-84%) and C18:3 cis-9,12,15 (-88%). In contrast to native bovine mammary gland tissue, MAC-T cells did not express SCD5. Expression of ACACA was increased by Ac (+44%) and reduced by C18:2 cis-9,12 (-48%) and C18:3 cis-9,12,15 (-49%). Compared with control, FASN expression was not significantly affected by the treatments. The mRNA level of SREBF1 was not affected by Ac or BHBA, but was reduced by C18:1 cis-9 (-44%), C18:1 trans-11 (-42%), C18:2 cis-9,12 (-62%) and C18:3 cis-9,12,15 (-68%) compared with control. Expression of INSIG1 was downregulated by C18:0 (-37%), C18:1 cis-9 (-63%), C18:1 trans-11 (-53%), C18:2 cis-9,12 (-81%) and C18:3 cis-9,12,15 (-91%). Both PPARA and PPARD expression were not significantly affected by the treatments. Our results show that Ac upregulated mRNA expression of SCD1 and ACACA in MAC-T cells. The opposite effect of the PUFA C18:2 cis-9,12 and C18:3 cis-9,12,15 on the these genes and the failure of Ac to mimic the PUFA-inhibited SREBF1 and INSIG1 mRNA expression, suggest that Ac can stimulate mammary lipogenesis via a transcriptional regulatory mechanism different from PUFA.
authors.affiliation: Animal Nutrition Group, Wageningen University, PO Box 338, 6700 AH Wageningen, The Netherlands.
authors.forename: A A A
authors.initials: AA
authors.lastname: Jacobs
authors.forename: J
authors.initials: J
authors.lastname: Dijkstra
authors.forename: J S
authors.initials: JS
authors.lastname: Liesman
authors.forename: M J
authors.initials: MJ
authors.lastname: Vandehaar
authors.forename: A L
authors.initials: AL
authors.lastname: Lock
authors.forename: A M
authors.initials: AM
authors.lastname: van Vuuren
authors.forename: W H
authors.initials: WH
authors.lastname: Hendriks
authors.forename: J
authors.initials: J
authors.lastname: van Baal
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000494:pharmacology; D019342:Acetic Acid / Q000494:pharmacology; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002417:Cattle; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004847:Epithelial Cells / Q000201:enzymology*; D064429:Fatty Acid Synthases / Q000378:metabolism; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D050155:Lipogenesis / Q000187:drug effects* / Q000235:genetics; D008321:Mammary Glands, Animal / Q000166:cytology*; D047493:PPAR alpha / Q000378:metabolism; D047494:PPAR delta / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism
chemical_list: D017931:DNA Primers; D005227:Fatty Acids; D047493:PPAR alpha; D047494:PPAR delta; D051780:Sterol Regulatory Element Binding Protein 1; D013230:Stearoyl-CoA Desaturase; D064429:Fatty Acid Synthases; D000103:Acetyl-CoA Carboxylase; D019342:Acetic Acid; D020155:3-Hydroxybutyric Acid