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

Pallavi Mukherjee; Greg Hough; Arnab Chattopadhyay; Victor Grijalva; Ellen Ines O'Connor; David Meriwether; Alan Wagner; James M. Ntambi; Mohamad Navab; Srinivasa T. Reddy; Alan M. Fogelman

Journal of Lipid Research (Oct 2018)

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

Pallavi Mukherjee,
Greg Hough,
Arnab Chattopadhyay,
Victor Grijalva,
Ellen Ines O'Connor,
David Meriwether,
Alan Wagner,
James M. Ntambi,
Mohamad Navab,
Srinivasa T. Reddy,
Alan M. Fogelman

Affiliations

Pallavi Mukherjee: Departments of Medicine, University of California-Los Angeles, Los Angeles, CA 90095
Greg Hough: Departments of Medicine, University of California-Los Angeles, Los Angeles, CA 90095
Arnab Chattopadhyay: Departments of Medicine, University of California-Los Angeles, Los Angeles, CA 90095
Victor Grijalva: Departments of Medicine, University of California-Los Angeles, Los Angeles, CA 90095
Ellen Ines O'Connor: Molecular Toxicology Interdepartmental Program, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095
David Meriwether: Departments of Molecular and Medical Pharmacology, University of California-Los Angeles, Los Angeles, CA 90095
Alan Wagner: Departments of Medicine, University of California-Los Angeles, Los Angeles, CA 90095
James M. Ntambi: Departments of Biochemistry and Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706
Mohamad Navab: Departments of Medicine, University of California-Los Angeles, Los Angeles, CA 90095
Srinivasa T. Reddy: To whom correspondence should be addressed.; Departments of Medicine, University of California-Los Angeles, Los Angeles, CA 90095; Departments of Molecular and Medical Pharmacology, University of California-Los Angeles, Los Angeles, CA 90095; Departments of Obstetrics and Gynecology, University of California-Los Angeles, Los Angeles, CA 90095; To whom correspondence should be addressed.
Alan M. Fogelman: Departments of Medicine, University of California-Los Angeles, Los Angeles, CA 90095

Journal volume & issue: Vol. 59, no. 10
pp. 1818 – 1840

Abstract

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After crossing floxed stearoyl-CoA desaturase-1 (Scd1fl/fl) mice with LDL receptor-null (ldlr−/−) mice, and then Villin Cre (VilCre) mice, enterocyte Scd1 expression in Scd1fl/fl/ldlr−/−/VilCre mice was reduced 70%. On Western diet (WD), Scd1fl/fl/ldlr−/− mice gained more weight than Scd1fl/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 Scd1fl/fl/ldlr−/−/VilCre compared with Scd1fl/fl/ldlr−/− mice (P < 0.0004 and P < 0.026, respectively). On WD, Scd1fl/fl/ldlr−/−/VilCre mice compared with Scd1fl/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 Scd1fl/fl/ldlr−/− mice similar to that seen in Scd1fl/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 Scd1fl/fl/ldlr−/− mice, but not in Scd1fl/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.

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

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