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

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) 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.

• Authors: 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: Journal of lipid research (J Lipid Res) Vol. 59 Issue 10 Pg. 1818-1840 (10 2018) ISSN: 1539-7262 [Electronic] United States
• PMID: 30139760 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Mukherjee et al.

Chemical References

• Acute-Phase Proteins
• Carrier Proteins
• Cholesterol, HDL
• Lipopolysaccharide Receptors
• Lysophosphatidylcholines
• Membrane Glycoproteins
• Myeloid Differentiation Factor 88
• Receptors, LDL
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• lipopolysaccharide-binding protein
• Scd1 protein, mouse
• Stearoyl-CoA Desaturase

Topics

• Acute-Phase Proteins (metabolism)
• Animals
• Body Weight
• Carrier Proteins (metabolism)
• Cholesterol, HDL (blood)
• Dyslipidemias (enzymology, genetics, metabolism)
• Enterocytes (enzymology)
• Female
• Gene Deletion
• Gene Expression Regulation, Enzymologic
• Gene Knockdown Techniques
• Jejunum (metabolism)
• Lipopolysaccharide Receptors (metabolism)
• Lysophosphatidylcholines (metabolism)
• Male
• Membrane Glycoproteins (metabolism)
• Mice
• Mice, Inbred C57BL
• Myeloid Differentiation Factor 88 (metabolism)
• Receptors, LDL (deficiency, genetics)
• Stearoyl-CoA Desaturase (deficiency, genetics, metabolism)
• Toll-Like Receptor 4 (metabolism)