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Duodenal Niemann-Pick C1-like 1 expression was negatively correlated with liver X receptor expression in nonalcoholic fatty liver disease

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Background/Aims: Intestinal cholesterol absorption includes intestinal Niemann- Pick C1-like 1 (NPC1L1) and is an important target pathway in nonalcoholic fatty liver disease (NAFLD). We investigated the expression of NPC1L1 and its correlation with liver X receptor (LXR) expression in peripheral mononuclear (PMN) cells in patients with NAFLD. Methods: We evaluated intestinal expression of NPC1L1 in 25 NAFLD patients and 28 healthy controls. We calculated the mRNA expression levels of LXR and farnesoid X receptor (FXR), which are master players of cholesterol metabolism in PMN cells. The protein expression of ABCA1, ABCG5/8, NPC1L1, SREBP, LXR, FXR, and CD36 was measured on tissue samples from the duodenum and ileum. Results: The expression of LXR (p = 0.01) and FXR (p = 0.03) in PMN cells was increased in the NAFLD group compared to the control group. Duodenal NPC1L1 decreased in the NAFLD group compared to the healthy controls (3.38 ± 1.4 vs. 2.42 ± 1.2, p = 0.05). NPC1L1 expression in the duodenum was negatively correlated with LXR expression in PMN cells. Expression of LXR and FXR in the ileum was also negatively correlated with the expression of LXR in PMN cells. Conclusions: Duodenal NPC1L1 expression was decreased in NAFLD and was negatively correlated with LXR expression in PMN cells.

Abstract

Background/Aims: Intestinal cholesterol absorption includes intestinal Niemann- Pick C1-like 1 (NPC1L1) and is an important target pathway in nonalcoholic fatty liver disease (NAFLD). We investigated the expression of NPC1L1 and its correlation with liver X receptor (LXR) expression in peripheral mononuclear (PMN) cells in patients with NAFLD. Methods: We evaluated intestinal expression of NPC1L1 in 25 NAFLD patients and 28 healthy controls. We calculated the mRNA expression levels of LXR and farnesoid X receptor (FXR), which are master players of cholesterol metabolism in PMN cells. The protein expression of ABCA1, ABCG5/8, NPC1L1, SREBP, LXR, FXR, and CD36 was measured on tissue samples from the duodenum and ileum. Results: The expression of LXR (p = 0.01) and FXR (p = 0.03) in PMN cells was increased in the NAFLD group compared to the control group. Duodenal NPC1L1 decreased in the NAFLD group compared to the healthy controls (3.38 ± 1.4 vs. 2.42 ± 1.2, p = 0.05). NPC1L1 expression in the duodenum was negatively correlated with LXR expression in PMN cells. Expression of LXR and FXR in the ileum was also negatively correlated with the expression of LXR in PMN cells. Conclusions: Duodenal NPC1L1 expression was decreased in NAFLD and was negatively correlated with LXR expression in PMN cells.

참고문헌 (28)

  1. Gylling H, "Cholesterol metabolism and its implications for therapeutic interventions in patients with hypercholesterolaemia", Int J Clin Pract, 58, pp.859~866 (2004)
  2. Koo SH, "Nonalcoholic fatty liver disease : molecular mechanisms for the hepatic steatosis", Clin Mol Hepatol, 19, pp.210~215 (2013)
  3. Altmann SW, "Niemann-Pick C1like 1 protein is critical for intestinal cholesterol absorption", Science, 303, pp.1201~1204 (2004)
  4. Davis HR Jr, "Niemann-Pick C1like 1(NPC1L1)is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis", J Biol Chem, 279, pp.33586~33592 (2004)
  5. Garcia-Calvo M, "The target of ezetimibe is Niemann-Pick C1-like 1(NPC1L1)", Proc Natl Acad Sci U S A, 102, pp.8132~8137 (2005)
  6. Nomura M, "Inhibition of hepatic Niemann-Pick C1-like 1 improves hepatic insulin resistance", Am J Physiol Endocrinol Metab, 297, pp.E1030~E1038 (2009)
  7. Ahn SB, "Expression of liver X receptor correlates with intrahepatic inflammation and fibrosis in patients with nonalcoholic fatty liver disease", Dig Dis Sci, 59, pp.2975~2982 (2014)
  8. Moschetta A, "Nuclear receptors and cholesterol metabolism in the intestine", Atheroscler Suppl, 17, pp.9~11 (2015)
  9. Bonamassa B, "Atherosclerosis : lessons from LXR and the intestine", Trends Endocrinol Metab, 24, pp.120~128 (2013)
  10. Chawla A, "Nuclear receptors and lipid physiology : opening the X-files", Science, 294, pp.1866~1870 (2001)
  11. Rebe C, "Induction of transglutaminase 2 by a liver X receptor", retinoic acid receptor alpha pathway increases the clearance of apoptotic cells by human macrophages, 2009, pp.105, 393~401
  12. DiBlasio-Smith EA, "Discovery and implementation of transcriptional biomarkers of synthetic LXR agonists in peripheral blood cells", J Transl Med, 6, pp.59~ (2008)
  13. Piekarski J, "Difference between liver and spleen CT numbers in the normal adult : its usefulness in predicting the presence of diffuse liver disease", Radiology, 137, pp.727~729 (1980)
  14. Bydder GM, "Computed tomography attenuation values in fatty liver", J Comput Tomogr, 5, pp.33~35 (1981)
  15. Sehayek E, "Cholesterol absorption from the intestine is a major determinant of reverse cholesterol transport from peripheral tissue macrophages", Arterioscler Thromb Vasc Biol, 28, pp.1296~1297 (2008)
  16. Simonen P, "Cholesterol synthesis is increased and absorption decreased in non-alcoholic fatty liver disease independent of obesity", J Hepatol, 54, pp.153~159 (2011)
  17. Yoneda M, "Efficacy of ezetimibe for the treatment of non-alcoholic steatohepatitis : an open-label, pilot study", Hepatol Res, 40, pp.566~573 (2010)
  18. Park H, "Efficacy of longterm ezetimibe therapy in patients with nonalcoholic fatty liver disease", J Gastroenterol, 46, pp.101~107 (2011)
  19. Korean Association for the Study of the Liver(KASL), "KASL clinical practice guidelines : management of nonalcoholic fatty liver disease", Clin Mol Hepatol, 19, pp.325~348 (2013)
  20. Kastelein JJ, "Simvastatin with or without ezetimibe in familial hypercholesterolemia", N Engl J Med, 358, pp.1431~1443 (2008)
  21. Tang W, "Niemann-Pick C1-like 1 is required for an LXR agonist to raise plasma HDL cholesterol in mice", Arterioscler Thromb Vasc Biol, 28, pp.448~454 (2008)
  22. Duval C, "Niemann-Pick C1like 1 gene expression is down-regulated by LXR activators in the intestine", Biochem Biophys Res Commun, 340, pp.1259~1263 (2006)
  23. Lo Sasso G, "Intestinal specific LXR activation stimulates reverse cholesterol transport and protects from atherosclerosis", Cell Metab, 12, pp.187~193 (2010)
  24. Vik-Mo AO, "Psychotropic drugs up-regulate the expression of cholesterol transport proteins including ApoE in cultured human CNS-and liver cells", BMC Pharmacol, 9, pp.10~ (2009)
  25. Calkin AC, "Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR", Nat Rev Mol Cell Biol, 13, pp.213~224 (2012)
  26. Schwenzer NF, "Non-invasive assessment and quantification of liver steatosis by ultrasound, computed tomography and magnetic resonance", J Hepatol, 51, pp.433~445 (2009)
  27. Park SH, "Macrovesicular hepatic steatosis in living liver donors : use of CT for quantitative and qualitative assessment", Radiology, 239, pp.105~112 (2006)
  28. Masson CJ, "Fatty acid-and cholesterol transporter protein expression along the human intestinal tract", PLoS One, 5, pp.e10380~ (2010)

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