The inhibitory effect of trans-10, cis-12 CLA on lipid synthesis in bovine mammary epithelial cells involves reduced proteolytic activation of the transcription factor SREBP-1.
The trans-10, cis-12 CLA isomer has been causally related to milk fat depression in dairy cows, although no molecular mechanism has been established. Sterol response element-binding protein (SREBP)-1 is a transcription factor synthesized and retained as a membrane-bound precursor in the endoplasmic reticulum and proteolytically cleaved to release an active fragment that migrates to the nucleus to stimulate lipogenic gene transcription. Certain lipid molecules (i.e., PUFA) were shown to inhibit the proteolytic activation of SREBP-1 in rodent liver models, although there has been no previous demonstration of its presence in bovine tissues or in mammary tissue of any species. We used a bovine mammary cell line (MAC-T) to assess the involvement of SREBP-1 in the regulation of lipid synthesis in bovine mammary cells by trans-10, cis-12 CLA. Treatment with 75 micromol/L trans-10, cis-12 CLA for 48 h resulted in an approximately 50% reduction of (14)C-acetate incorporation into total lipid and corresponding reductions in mRNA abundance for acetyl CoA carboxylase, fatty acid synthase, and stearoyl CoA desaturase, whereas cis-9, trans-11 CLA had no effect on these genes. There was no reduction in SREBP-1 mRNA or precursor protein, but the abundance of the activated nuclear fragment of the protein was significantly reduced by treatment with 75 micromol/L trans-10, cis-12 CLA. These results indicate that trans-10, cis-12 CLA reduces lipid synthesis in the bovine mammary gland through inhibition of the proteolytic activation of SREBP-1 and subsequent reduction in transcriptional activation of lipogenic genes.
Peterson
Daniel G
DG
Department of Animal Science, Cornell University, Ithaca, NY 14853, USA.
Matitashvili
Elvina A
EA
Bauman
Dale E
DE
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002417:Cattle; D002460:Cell Line; D004268:DNA-Binding Proteins; D023281:Genomics; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008055:Lipids / Q000096:biosynthesis*; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D044243:Linoleic Acids, Conjugated; D008055:Lipids; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors