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Role of enterocyte stearoyl-Co-A desaturase-1 in LDLR-null mice.
Mukherjee, Pallavi; Hough, Greg; Chattopadhyay, Arnab; Grijalva, Victor; O'Connor, Ellen Ines; Meriwether, David; Wagner, Alan; Ntambi, James M; Navab, Mohamad; Reddy, Srinivasa T; Fogelman, Alan M.
Afiliação
  • Mukherjee P; Departments of Medicine, University of California-Los Angeles, Los Angeles, CA 90095.
  • Hough G; Departments of Medicine, University of California-Los Angeles, Los Angeles, CA 90095.
  • Chattopadhyay A; Departments of Medicine, University of California-Los Angeles, Los Angeles, CA 90095.
  • Grijalva V; Departments of Medicine, University of California-Los Angeles, Los Angeles, CA 90095.
  • O'Connor EI; Molecular Toxicology Interdepartmental Program, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095.
  • Meriwether D; Departments of Molecular and Medical Pharmacology, University of California-Los Angeles, Los Angeles, CA 90095.
  • Wagner A; Departments of Medicine, University of California-Los Angeles, Los Angeles, CA 90095.
  • Ntambi JM; Departments of Biochemistry and Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706.
  • Navab M; Departments of Medicine, University of California-Los Angeles, Los Angeles, CA 90095.
  • Reddy ST; Departments of Medicine, University of California-Los Angeles, Los Angeles, CA 90095 sreddy@mednet.ucla.edu.
  • Fogelman AM; Departments of Molecular and Medical Pharmacology, University of California-Los Angeles, Los Angeles, CA 90095.
J Lipid Res ; 59(10): 1818-1840, 2018 10.
Article em En | MEDLINE | ID: mdl-30139760
ABSTRACT
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) 181 and lysophosphatidic acid (LPA) 181 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 181 to WD did not reverse the effects of enterocyte Scd1 knockdown. Adding LysoPC 181 (but not LysoPC 180) 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 181- and WD-induced dyslipidemia and inflammation in ldlr-/- mice.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Estearoil-CoA Dessaturase / Receptores de LDL / Deleção de Genes / Enterócitos Limite: Animals Idioma: En Revista: J Lipid Res Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Estearoil-CoA Dessaturase / Receptores de LDL / Deleção de Genes / Enterócitos Limite: Animals Idioma: En Revista: J Lipid Res Ano de publicação: 2018 Tipo de documento: Article