Expression of Liver X Receptor Correlates with Intrahepatic Inflammation and Fibrosis in Patients with Nonalcoholic Fatty Liver Disease

Sang Bong Ahn, Kiseok Jang, Dae Won Jung, Byung Hoon Lee, Kye Jung Shin

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Background: Liver X receptor (LXR) is an oxysterol-activated nuclear receptor involved in the control of major metabolic pathways for cholesterol homeostasis and lipogenesis. Although the role of LXR in hepatic steatosis is well known, its correlation with intrahepatic inflammation and fibrosis has not been thoroughly studied. We investigated the association between LXRα, hepatic inflammation, and fibrosis, as well as its correlation with other intrahepatic lipid transporters in patients with nonalcoholic fatty liver disease (NAFLD).

Methods: We evaluated clinical characteristics including sex, age, body mass index, and laboratory findings from 40 NAFLD and 16 control patients. Immunohistochemical staining was carried out on liver biopsy samples from all patients.

Results: The positive rate of LXRα expression was 30 % in the control group, 50 % in the NAFLD group, and 97 % in NASH groups. LXRα expression was positively correlated with not only the amount of intrahepatic fat, but also with intrahepatic inflammation and hepatic fibrosis. LXRα expression showed positive correlation with intrahepatic expression of ABCG5/8, CD36, and SREBP-1c. The expression of ABCA1, ABCG5/8, SREBP-1c, and CD36 was higher in NAFLD than in controls and there was no further increase in the NASH group. NPC1L1 was abundant in human liver. Expression of NPC1L1 was negatively correlated with intrahepatic inflammation and LXRα intensity.

Conclusion: LXR expression correlated with the degree of hepatic fat deposition, as well as with hepatic inflammation and fibrosis in NAFLD patients. Our research suggests that LXR is an attractive target for treatment and regulation of hepatic inflammation and fibrosis.

Original languageEnglish
Pages (from-to)2975-2982
Number of pages8
JournalDigestive Diseases and Sciences
Volume59
Issue number12
DOIs
StatePublished - 2014 Nov 19

Fingerprint

Fibrosis
Inflammation
Liver
Sterol Regulatory Element Binding Protein 1
Fats
Liver X Receptors
Non-alcoholic Fatty Liver Disease
Lipogenesis
Metabolic Networks and Pathways
Sex Characteristics
Body Mass Index
Homeostasis
Cholesterol
Staining and Labeling
Lipids
Biopsy
Control Groups
Research

Keywords

  • Hepatic fibrosis
  • Liver X receptor
  • Nonalcoholic fatty liver disease
  • Nonalcoholic steatohepatitis

Cite this

@article{261a17d84d2d4662a2b2541e6f754c53,
title = "Expression of Liver X Receptor Correlates with Intrahepatic Inflammation and Fibrosis in Patients with Nonalcoholic Fatty Liver Disease",
abstract = "Background: Liver X receptor (LXR) is an oxysterol-activated nuclear receptor involved in the control of major metabolic pathways for cholesterol homeostasis and lipogenesis. Although the role of LXR in hepatic steatosis is well known, its correlation with intrahepatic inflammation and fibrosis has not been thoroughly studied. We investigated the association between LXRα, hepatic inflammation, and fibrosis, as well as its correlation with other intrahepatic lipid transporters in patients with nonalcoholic fatty liver disease (NAFLD).Methods: We evaluated clinical characteristics including sex, age, body mass index, and laboratory findings from 40 NAFLD and 16 control patients. Immunohistochemical staining was carried out on liver biopsy samples from all patients.Results: The positive rate of LXRα expression was 30 {\%} in the control group, 50 {\%} in the NAFLD group, and 97 {\%} in NASH groups. LXRα expression was positively correlated with not only the amount of intrahepatic fat, but also with intrahepatic inflammation and hepatic fibrosis. LXRα expression showed positive correlation with intrahepatic expression of ABCG5/8, CD36, and SREBP-1c. The expression of ABCA1, ABCG5/8, SREBP-1c, and CD36 was higher in NAFLD than in controls and there was no further increase in the NASH group. NPC1L1 was abundant in human liver. Expression of NPC1L1 was negatively correlated with intrahepatic inflammation and LXRα intensity.Conclusion: LXR expression correlated with the degree of hepatic fat deposition, as well as with hepatic inflammation and fibrosis in NAFLD patients. Our research suggests that LXR is an attractive target for treatment and regulation of hepatic inflammation and fibrosis.",
keywords = "Hepatic fibrosis, Liver X receptor, Nonalcoholic fatty liver disease, Nonalcoholic steatohepatitis",
author = "Ahn, {Sang Bong} and Kiseok Jang and Jung, {Dae Won} and Lee, {Byung Hoon} and Shin, {Kye Jung}",
year = "2014",
month = "11",
day = "19",
doi = "10.1007/s10620-014-3289-x",
language = "English",
volume = "59",
pages = "2975--2982",
journal = "Digestive Diseases and Sciences",
issn = "0163-2116",
number = "12",

}

Expression of Liver X Receptor Correlates with Intrahepatic Inflammation and Fibrosis in Patients with Nonalcoholic Fatty Liver Disease. / Ahn, Sang Bong; Jang, Kiseok; Jung, Dae Won; Lee, Byung Hoon; Shin, Kye Jung.

In: Digestive Diseases and Sciences, Vol. 59, No. 12, 19.11.2014, p. 2975-2982.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Expression of Liver X Receptor Correlates with Intrahepatic Inflammation and Fibrosis in Patients with Nonalcoholic Fatty Liver Disease

AU - Ahn, Sang Bong

AU - Jang, Kiseok

AU - Jung, Dae Won

AU - Lee, Byung Hoon

AU - Shin, Kye Jung

PY - 2014/11/19

Y1 - 2014/11/19

N2 - Background: Liver X receptor (LXR) is an oxysterol-activated nuclear receptor involved in the control of major metabolic pathways for cholesterol homeostasis and lipogenesis. Although the role of LXR in hepatic steatosis is well known, its correlation with intrahepatic inflammation and fibrosis has not been thoroughly studied. We investigated the association between LXRα, hepatic inflammation, and fibrosis, as well as its correlation with other intrahepatic lipid transporters in patients with nonalcoholic fatty liver disease (NAFLD).Methods: We evaluated clinical characteristics including sex, age, body mass index, and laboratory findings from 40 NAFLD and 16 control patients. Immunohistochemical staining was carried out on liver biopsy samples from all patients.Results: The positive rate of LXRα expression was 30 % in the control group, 50 % in the NAFLD group, and 97 % in NASH groups. LXRα expression was positively correlated with not only the amount of intrahepatic fat, but also with intrahepatic inflammation and hepatic fibrosis. LXRα expression showed positive correlation with intrahepatic expression of ABCG5/8, CD36, and SREBP-1c. The expression of ABCA1, ABCG5/8, SREBP-1c, and CD36 was higher in NAFLD than in controls and there was no further increase in the NASH group. NPC1L1 was abundant in human liver. Expression of NPC1L1 was negatively correlated with intrahepatic inflammation and LXRα intensity.Conclusion: LXR expression correlated with the degree of hepatic fat deposition, as well as with hepatic inflammation and fibrosis in NAFLD patients. Our research suggests that LXR is an attractive target for treatment and regulation of hepatic inflammation and fibrosis.

AB - Background: Liver X receptor (LXR) is an oxysterol-activated nuclear receptor involved in the control of major metabolic pathways for cholesterol homeostasis and lipogenesis. Although the role of LXR in hepatic steatosis is well known, its correlation with intrahepatic inflammation and fibrosis has not been thoroughly studied. We investigated the association between LXRα, hepatic inflammation, and fibrosis, as well as its correlation with other intrahepatic lipid transporters in patients with nonalcoholic fatty liver disease (NAFLD).Methods: We evaluated clinical characteristics including sex, age, body mass index, and laboratory findings from 40 NAFLD and 16 control patients. Immunohistochemical staining was carried out on liver biopsy samples from all patients.Results: The positive rate of LXRα expression was 30 % in the control group, 50 % in the NAFLD group, and 97 % in NASH groups. LXRα expression was positively correlated with not only the amount of intrahepatic fat, but also with intrahepatic inflammation and hepatic fibrosis. LXRα expression showed positive correlation with intrahepatic expression of ABCG5/8, CD36, and SREBP-1c. The expression of ABCA1, ABCG5/8, SREBP-1c, and CD36 was higher in NAFLD than in controls and there was no further increase in the NASH group. NPC1L1 was abundant in human liver. Expression of NPC1L1 was negatively correlated with intrahepatic inflammation and LXRα intensity.Conclusion: LXR expression correlated with the degree of hepatic fat deposition, as well as with hepatic inflammation and fibrosis in NAFLD patients. Our research suggests that LXR is an attractive target for treatment and regulation of hepatic inflammation and fibrosis.

KW - Hepatic fibrosis

KW - Liver X receptor

KW - Nonalcoholic fatty liver disease

KW - Nonalcoholic steatohepatitis

UR - http://www.scopus.com/inward/record.url?scp=84912525212&partnerID=8YFLogxK

U2 - 10.1007/s10620-014-3289-x

DO - 10.1007/s10620-014-3289-x

M3 - Article

C2 - 25102981

AN - SCOPUS:84912525212

VL - 59

SP - 2975

EP - 2982

JO - Digestive Diseases and Sciences

JF - Digestive Diseases and Sciences

SN - 0163-2116

IS - 12

ER -