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

First Author  Mukherjee P Year  2018
Journal  J Lipid Res Volume  59
Issue  10 Pages  1818-1840
PubMed ID  30139760 Mgi Jnum  J:266230
Mgi Id  MGI:6200973 Doi  10.1194/jlr.M083527
Citation  Mukherjee P, et al. (2018) Role of enterocyte stearoyl-Co-A desaturase-1 in LDLR-null mice. J Lipid Res 59(10):1818-1840
abstractText  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.
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