Regulation of sterol regulatory element-binding proteins (SREBPs) by fatty acid flux was investigated in CaCo-2 cells. Cells were incubated with 1mM taurocholate with or without 250μM 18:0, 18:1, 18:2, 20:4, 20:5 or 22:6 fatty acids. Fatty acid synthase (FAS) and acetyl-CoA carboxylase mRNA levels and gene and protein expression of SREBPs were estimated. 18:2, 20:4, 20:5 and 22:6 fatty acids decreased the amount of mature SREBP-1 and mRNA levels of SREBP-1c, SREBP-1a, FAS and acetyl-CoA carboxylase. SREBP-2 gene or mature protein expression was not altered. Liver X receptor (LXR) activation by T0901317 increased gene expression of SREBP-1c, SREBP-1a, FAS and acetyl-CoA carboxylase without altering SREBP-2. 20:5, but not 18:1, prevented the full expression of SREBP-1c mRNA by T0901317. T0901317 increased SREBP-1 mass without altering the mass of mature SREBP-2. Although only 18:2, 20:4, 20:5 and 22:6 suppressed SREBP-1, acetyl-CoA carboxylase and FAS expression, all fatty acids decreased the rate of fatty acid synthesis. T0901317 increased endogenous fatty acid synthesis yet did not increase secretion of triacylglycerol-rich lipoproteins. In CaCo-2 cells, polyunsaturated fatty acids decrease gene and protein expression of SREBP-1 and FAS mRNA, probably through interference with LXR activity. Since all fatty acids decreased fatty acid synthesis, mechanisms other than changes in SREBP-1c expression must be entertained. Increased endogenous fatty acid synthesis does not promote triacylglycerol-rich lipoprotein secretion.
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December 2002
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Research Article|
December 15 2002
Polyunsaturated fatty acids decrease the expression of sterol regulatory element-binding protein-1 in CaCo-2 cells: effect on fatty acid synthesis and triacylglycerol transport
F. Jeffrey FIELD
;
F. Jeffrey FIELD
1
∗Department of Veterans Affairs, Iowa City, IA 52242, U.S.A.,
†Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, U.S.A.
1To whom correspondence should be addressed, at the Department of Internal Medicine (e-mail f-jeffrey-field@uiowa.edu).
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Ella BORN
;
Ella BORN
∗Department of Veterans Affairs, Iowa City, IA 52242, U.S.A.,
†Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, U.S.A.
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Shubha MURTHY
;
Shubha MURTHY
∗Department of Veterans Affairs, Iowa City, IA 52242, U.S.A.,
†Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, U.S.A.
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Satya N. MATHUR
Satya N. MATHUR
∗Department of Veterans Affairs, Iowa City, IA 52242, U.S.A.,
†Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, U.S.A.
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Biochem J (2002) 368 (3): 855–864.
Article history
Received:
May 08 2002
Revision Received:
August 21 2002
Accepted:
September 04 2002
Accepted Manuscript online:
September 04 2002
Citation
F. Jeffrey FIELD, Ella BORN, Shubha MURTHY, Satya N. MATHUR; Polyunsaturated fatty acids decrease the expression of sterol regulatory element-binding protein-1 in CaCo-2 cells: effect on fatty acid synthesis and triacylglycerol transport. Biochem J 15 December 2002; 368 (3): 855–864. doi: https://doi.org/10.1042/bj20020731
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