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

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.

[1]  S. Reddy,et al.  Treating the Intestine with Oral ApoA-I Mimetic Tg6F Reduces Tumor Burden in Mouse Models of Metastatic Lung Cancer , 2018, Scientific Reports.

[2]  Bo Wang,et al.  ER phospholipid composition modulates lipogenesis during feeding and in obesity. , 2017, The Journal of clinical investigation.

[3]  A. Lusis,et al.  Transgenic tomatoes expressing the 6F peptide and ezetimibe prevent diet-induced increases of IFN-β and cholesterol 25-hydroxylase in jejunum , 2017, Journal of Lipid Research.

[4]  Karen J. Kieser,et al.  Multi-receptor detection of individual bacterial products by the innate immune system , 2017, Nature Reviews Immunology.

[5]  A. Lusis,et al.  Transgenic Tomatoes Expressing the 6 F Peptide and Ezetimibe Prevent Diet-induced Increases of Interferon-b and Cholesterol 25-hydroxylase in Jejunum , 2017 .

[6]  D. Hui.  Intestinal phospholipid and lysophospholipid metabolism in cardiometabolic disease , 2016, Current opinion in lipidology.

[7]  A. Lusis,et al.  Tg6F ameliorates the increase in oxidized phospholipids in the jejunum of mice fed unsaturated LysoPC or WD[S] , 2016, Journal of Lipid Research.

[8]  E. Gratton,et al.  Intestinal Phospholipid Remodeling Is Required for Dietary-Lipid Uptake and Survival on a High-Fat Diet. , 2016, Cell metabolism.

[9]  P. Nighot,et al.  Lipopolysaccharide Regulation of Intestinal Tight Junction Permeability Is Mediated by TLR4 Signal Transduction Pathway Activation of FAK and MyD88 , 2015, The Journal of Immunology.

[10]  Feng Su,et al.  Efficacy of tomato concentrates in mouse models of dyslipidemia and cancer , 2015, Pharmacology research & perspectives.

[11]  Feng Su,et al.  Source and role of intestinally derived lysophosphatidic acid in dyslipidemia and atherosclerosis , 2015, Journal of Lipid Research.

[12]  F. Gao,et al.  Transgenic 6F tomatoes act on the small intestine to prevent systemic inflammation and dyslipidemia caused by Western diet and intestinally derived lysophosphatidic acid[S] , 2013, Journal of Lipid Research.

[13]  P. Edwards,et al.  LXRs regulate ER stress and inflammation through dynamic modulation of membrane phospholipid composition. , 2013, Cell metabolism.

[14]  C. Glass,et al.  25-Hydroxycholesterol Activates the Integrated Stress Response to Reprogram Transcription and Translation in Macrophages* , 2013, The Journal of Biological Chemistry.

[15]  James R. Springstead,et al.  A novel approach to oral apoA-I mimetic therapy[S] , 2013, Journal of Lipid Research.

[16]  Dong-Hyun Kim,et al.  High Fat Diet-Induced Gut Microbiota Exacerbates Inflammation and Obesity in Mice via the TLR4 Signaling Pathway , 2012, PloS one.

[17]  J. Ntambi,et al.  Combined deletion of SCD1 from adipose tissue and liver does not protect mice from obesity[S] , 2012, Journal of Lipid Research.

[18]  S. Reddy,et al.  D-4F-mediated reduction in metabolites of arachidonic and linoleic acids in the small intestine is associated with decreased inflammation in low-density lipoprotein receptor-null mice[S] , 2012, Journal of Lipid Research.

[19]  J. Ntambi,et al.  Adipose-specific deletion of stearoyl-CoA desaturase 1 up-regulates the glucose transporter GLUT1 in adipose tissue. , 2010, Biochemical and biophysical research communications.

[20]  Yong-ping Su,et al.  Normalizing genes for real-time polymerase chain reaction in epithelial and nonepithelial cells of mouse small intestine. , 2010, Analytical biochemistry.

[21]  S. Servi,et al.  Synthesis of Lysophospholipids , 2010, Molecules.

[22]  Maria T. Abreu,et al.  Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function , 2010, Nature Reviews Immunology.

[23]  Kiki Chu,et al.  Skin-specific Deletion of Stearoyl-CoA Desaturase-1 Alters Skin Lipid Composition and Protects Mice from High Fat Diet-induced Obesity* , 2009, The Journal of Biological Chemistry.

[24]  B. McManus,et al.  Despite Antiatherogenic Metabolic Characteristics, SCD1-Deficient Mice Have Increased Inflammation and Atherosclerosis , 2009, Arteriosclerosis, thrombosis, and vascular biology.

[25]  Heather M. Alger,et al.  Inhibition of Stearoyl-Coenzyme A Desaturase 1 Dissociates Insulin Resistance and Obesity From Atherosclerosis , 2008, Circulation.

[26]  Takao Shimizu,et al.  Discovery of a lysophospholipid acyltransferase family essential for membrane asymmetry and diversity , 2008, Proceedings of the National Academy of Sciences.

[27]  M. Hayden,et al.  Absence of stearoyl-CoA desaturase-1 ameliorates features of the metabolic syndrome in LDLR-deficient mice Published, JLR Papers in Press, October 24, 2007. , 2008, Journal of Lipid Research.

[28]  M. Miyazaki,et al.  Hepatic stearoyl-CoA desaturase-1 deficiency protects mice from carbohydrate-induced adiposity and hepatic steatosis. , 2007, Cell metabolism.

[29]  M. Miyazaki,et al.  Colocalization of SCD1 and DGAT2: implying preference for endogenous monounsaturated fatty acids in triglyceride synthesis Published, JLR Papers in Press, June 2, 2006. , 2006, Journal of Lipid Research.

[30]  G. Getz,et al.  Diet and Murine Atherosclerosis , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[31]  M. Miyazaki,et al.  Dietary cholesterol opposes PUFA-mediated repression of the stearoyl-CoA desaturase-1 gene by SREBP-1 independent mechanism DOI 10.1194/jlr.M100433-JLR200 , 2002, Journal of Lipid Research.

[32]  F. Kuipers,et al.  Fat malabsorption in essential fatty acid-deficient mice is not due to impaired bile formation , 2002 .

[33]  B. Yandell,et al.  Loss of stearoyl–CoA desaturase-1 function protects mice against adiposity , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Dietlind Adlercreutz,et al.  Synthesis of phosphatidylcholine with defined fatty acid in the sn-1 position by lipase-catalyzed esterification and transesterification reaction. , 2002, Biotechnology and bioengineering.

[35]  M. Miyazaki,et al.  The Biosynthesis of Hepatic Cholesterol Esters and Triglycerides Is Impaired in Mice with a Disruption of the Gene for Stearoyl-CoA Desaturase 1* , 2000, The Journal of Biological Chemistry.

[36]  C. T. Park,et al.  Plasma Lipopolysaccharide-binding Protein Is Found Associated with a Particle Containing Apolipoprotein A-I, Phospholipid, and Factor H-related Proteins* , 1996, The Journal of Biological Chemistry.

[37]  M. Wurfel,et al.  Lipopolysaccharide (LPS)-binding protein is carried on lipoproteins and acts as a cofactor in the neutralization of LPS , 1994, The Journal of experimental medicine.