TY - JOUR
T1 - Regulation of Stearoyl-Coenzyme A Desaturase 1 by trans-10, cis-12 Conjugated Linoleic Acid via SREBP1 in Primary Goat Mammary Epithelial Cells
AU - Zhang, Tianying
AU - Li, Cong
AU - Huang, Lian
AU - Song, Ning
AU - Cao, Yanhong
AU - Loor, Juan J.
AU - Luo, Jun
AU - Shi, Huaiping
N1 - Funding Information:
*E-mail: luojun@nwsuaf.edu.cn. Tel.: +86-29-8708-2891. Fax: +86-29-8708-2892 (J.L.). *E-mail: huaipingshi@nwsuaf.edu.cn. Tel.: +86-29-8709-2102. Fax: +86-29-8709-2164 (H.S.). ORCID Jun Luo: 0000-0002-2597-3613 Huaiping Shi: 0000-0003-0476-7615 Author Contributions ¶T.Z. and C.L. contributed equally. Funding This research was jointly supported by the National Natural Science Foundation of China (31272409), the National PostDoctoral Science Foundation of China (2017M613230), and the Science Foundation of Shaanxi Province of China (2013KTZB02-02-03 and 2016KTZDNY02-05). Notes The authors declare no competing financial interest.
PY - 2019/2/6
Y1 - 2019/2/6
N2 - trans-10,cis-12 Conjugated linoleic acid (t10c12-CLA) is a biohydrogenation intermediate in the rumen that inhibits mammary fatty acid de novo synthesis in lactating dairy goats. However, the underlying molecular pathways in milk-lipid metabolism affected by t10c12-CLA are not completely understood. The present study investigated the lipid-regulation mechanisms in goat mammary epithelial cells (GMECs) in response to t10c12-CLA. Gene-expression analysis indicated sterol-regulatory-element-binding transcription factor1 (SREBF1) and its putative target gene stearoyl-CoA desaturase (SCD1) were down-regulated (fold changes of 0.33 ± 0.04, P < 0.05, and 0.19 ± 0.01, P < 0.01, respectively). Concentrations of cellular palmitoleic acid (C16:1) and oleic acid (C18:1) were decreased (1.12 ± 0.05 vs 1.69 ± 0.11% and 15.70 ± 0.44 vs 24.97 ± 0.82%, respectively, P < 0.01), whereas those of linoleic acid (C18:2) were increased (5.00 ± 0.14 vs 3.81 ± 0.25%, P < 0.05); the desaturation indices of C16 and C18 were decreased in response to t10c12-CLA treatment (6.90 ± 0.05 vs 8.00 ± 0.30% and 61.41 ± 0.65 vs 67.73 ± 1.33%, respectively, P < 0.05). A luciferase-activity assay indicated that deletion of the sterol-response-element (SRE) site and the nuclear-factor (NF-Y) site in the SCD1-promoter region (-511/+65 bp) suppressed the regulatory effect of t10c12-CLA. Overexpression of SREBF1 partly counteracted the inhibitory effect of t10c12-CLA on de novo fatty acid synthesis. Overall, t10c12-CLA causes an inhibition of fatty acid synthesis and desaturation and regulates SCD1 expression by affecting the binding of SREBP1 protein to the SRE and NF-Y sites.
AB - trans-10,cis-12 Conjugated linoleic acid (t10c12-CLA) is a biohydrogenation intermediate in the rumen that inhibits mammary fatty acid de novo synthesis in lactating dairy goats. However, the underlying molecular pathways in milk-lipid metabolism affected by t10c12-CLA are not completely understood. The present study investigated the lipid-regulation mechanisms in goat mammary epithelial cells (GMECs) in response to t10c12-CLA. Gene-expression analysis indicated sterol-regulatory-element-binding transcription factor1 (SREBF1) and its putative target gene stearoyl-CoA desaturase (SCD1) were down-regulated (fold changes of 0.33 ± 0.04, P < 0.05, and 0.19 ± 0.01, P < 0.01, respectively). Concentrations of cellular palmitoleic acid (C16:1) and oleic acid (C18:1) were decreased (1.12 ± 0.05 vs 1.69 ± 0.11% and 15.70 ± 0.44 vs 24.97 ± 0.82%, respectively, P < 0.01), whereas those of linoleic acid (C18:2) were increased (5.00 ± 0.14 vs 3.81 ± 0.25%, P < 0.05); the desaturation indices of C16 and C18 were decreased in response to t10c12-CLA treatment (6.90 ± 0.05 vs 8.00 ± 0.30% and 61.41 ± 0.65 vs 67.73 ± 1.33%, respectively, P < 0.05). A luciferase-activity assay indicated that deletion of the sterol-response-element (SRE) site and the nuclear-factor (NF-Y) site in the SCD1-promoter region (-511/+65 bp) suppressed the regulatory effect of t10c12-CLA. Overexpression of SREBF1 partly counteracted the inhibitory effect of t10c12-CLA on de novo fatty acid synthesis. Overall, t10c12-CLA causes an inhibition of fatty acid synthesis and desaturation and regulates SCD1 expression by affecting the binding of SREBP1 protein to the SRE and NF-Y sites.
KW - SCD1
KW - SREBP1
KW - fatty acid
KW - mammary
KW - t10c12-CLA
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U2 - 10.1021/acs.jafc.8b06358
DO - 10.1021/acs.jafc.8b06358
M3 - Article
C2 - 30644742
AN - SCOPUS:85061117612
VL - 67
SP - 1463
EP - 1469
JO - Journal of Agricultural and Food Chemistry
JF - Journal of Agricultural and Food Chemistry
SN - 0021-8561
IS - 5
ER -