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J Lipid Res. 2018 Oct;59(10):1818-1840. doi: 10.1194/jlr.M083527. Epub 2018 Aug 23.

Role of enterocyte stearoyl-Co-A desaturase-1 in LDLR-null mice.

Author information

1
Departments of Medicine, University of California-Los Angeles, Los Angeles, CA 90095.
2
Molecular Toxicology Interdepartmental Program, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095.
3
Departments of Molecular and Medical Pharmacology, University of California-Los Angeles, Los Angeles, CA 90095.
4
Departments of Biochemistry and Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706.
5
Departments of Medicine, University of California-Los Angeles, Los Angeles, CA 90095 sreddy@mednet.ucla.edu.
6
Departments of Obstetrics and Gynecology, University of California-Los Angeles, Los Angeles, CA 90095.

Abstract

After crossing floxed stearoyl-CoA desaturase-1 (Scd1 fl/fl) mice with LDL receptor-null (ldlr -/-) mice, and then Villin Cre (VilCre) mice, enterocyte Scd1 expression in Scd1 fl/fl/ldlr -/-/VilCre mice was reduced 70%. On Western diet (WD), Scd1 fl/fl/ldlr -/- mice gained more weight than Scd1 fl/fl/ldlr -/-/VilCre mice (P < 0.0023). On WD, jejunum levels of lysophosphatidylcholine (LysoPC) 18:1 and lysophosphatidic acid (LPA) 18:1 were significantly less in Scd1 fl/fl/ldlr -/-/VilCre compared with Scd1 fl/fl/ldlr -/- mice (P < 0.0004 and P < 0.026, respectively). On WD, Scd1 fl/fl/ldlr -/-/VilCre mice compared with Scd1 fl/fl/ldlr -/- mice had lower protein levels of lipopolysaccharide-binding protein (LBP), cluster of differentiation 14 (CD14), toll-like receptor 4 (TLR4), and myeloid differentiation factor-88 (MyD88) in enterocytes and plasma, and less dyslipidemia and systemic inflammation. Adding a concentrate of tomatoes transgenic for the apoA-I mimetic peptide 6F (Tg6F) to WD resulted in reduced enterocyte protein levels of LBP, CD14, TLR4, and MyD88 in Scd1 fl/fl/ldlr -/- mice similar to that seen in Scd1 fl/fl/ldlr -/-/VilCre mice. Adding LysoPC 18:1 to WD did not reverse the effects of enterocyte Scd1 knockdown. Adding LysoPC 18:1 (but not LysoPC 18:0) to chow induced jejunum Scd1 expression and increased dyslipidemia and plasma serum amyloid A and interleukin 6 levels in Scd1 fl/fl/ldlr -/- mice, but not in Scd1 fl/fl/ldlr -/-/VilCre mice. We conclude that enterocyte Scd1 is partially responsible for LysoPC 18:1- and WD-induced dyslipidemia and inflammation in ldlr -/- mice.

KEYWORDS:

Tg6F; apolipoprotein A-I mimetic peptides; atherosclerosis; cluster of differentiation 14; coenzyme A; lipopolysaccharide-binding protein; low density lipoprotein receptor-null; toll-like receptor 4

PMID:
30139760
PMCID:
PMC6168294
[Available on 2019-10-01]
DOI:
10.1194/jlr.M083527
[Indexed for MEDLINE]

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