New insights into the role of Lith genes in the formation of cholesterol-supersaturated bile

Helen H. Wang, Tiangang Li, Piero Portincasa, David A. Ford, Brent A. Neuschwander-Tetri, Patrick Tso, David Q.H. Wang

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Cholesterol gallstone formation represents a failure of biliary cholesterol homeostasis in which the physical-chemical balance of cholesterol solubility in bile is disturbed. Lithogenic bile is mainly caused by persistent hepatic hypersecretion of biliary cholesterol and sustained cholesterol-supersaturated bile is an essential prerequisite for the precipitation of solid cholesterol monohydrate crystals and the formation of cholesterol gallstones. The metabolic determinants of the supply of hepatic cholesterol molecules that are recruited for biliary secretion are dependent upon the input-output balance of cholesterol and its catabolism in the liver. The sources of cholesterol for hepatic secretion into bile have been extensively investigated; however, to what extent each cholesterol source contributes to hepatic secretion is still unclear both under normal physiological conditions and in the lithogenic state. Although it has been long known that biliary lithogenicity is initiated by hepatic cholesterol hypersecretion, the genetic mechanisms that cause supersaturated bile have not been defined yet. Identification of the Lith genes that determine hepatic cholesterol hypersecretion should provide novel insights into the primary genetic and pathophysiological defects for gallstone formation. In this review article, we focus mainly on the pathogenesis of the formation of supersaturated bile and gallstones from the viewpoint of genetics and pathophysiology. A better understanding of the molecular genetics and pathophysiology of the formation of cholesterol-supersaturated bile will undoubtedly facilitate the development of novel, effective, and noninvasive therapies for patients with gallstones, which would reduce the morbidity, mortality, and costs of health care associated with gallstones, a very prevalent liver disease worldwide.

Original languageEnglish (US)
Pages (from-to)42-53
Number of pages12
JournalLiver Research
Volume1
Issue number1
DOIs
StatePublished - Jun 2017
Externally publishedYes

Fingerprint

Bile
Cholesterol
Gallstones
Genes
Liver
Health Care Costs
Solubility
Liver Diseases
Molecular Biology
Homeostasis

Keywords

  • Bile acid
  • Bile flow
  • Biliary secretion
  • Lith gene
  • Micelle
  • Vesicle

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

New insights into the role of Lith genes in the formation of cholesterol-supersaturated bile. / Wang, Helen H.; Li, Tiangang; Portincasa, Piero; Ford, David A.; Neuschwander-Tetri, Brent A.; Tso, Patrick; Wang, David Q.H.

In: Liver Research, Vol. 1, No. 1, 06.2017, p. 42-53.

Research output: Contribution to journalReview article

Wang, HH, Li, T, Portincasa, P, Ford, DA, Neuschwander-Tetri, BA, Tso, P & Wang, DQH 2017, 'New insights into the role of Lith genes in the formation of cholesterol-supersaturated bile', Liver Research, vol. 1, no. 1, pp. 42-53. https://doi.org/10.1016/j.livres.2017.05.005
Wang, Helen H. ; Li, Tiangang ; Portincasa, Piero ; Ford, David A. ; Neuschwander-Tetri, Brent A. ; Tso, Patrick ; Wang, David Q.H. / New insights into the role of Lith genes in the formation of cholesterol-supersaturated bile. In: Liver Research. 2017 ; Vol. 1, No. 1. pp. 42-53.
@article{9bd25301fd1a49d6b170ea0f652d640f,
title = "New insights into the role of Lith genes in the formation of cholesterol-supersaturated bile",
abstract = "Cholesterol gallstone formation represents a failure of biliary cholesterol homeostasis in which the physical-chemical balance of cholesterol solubility in bile is disturbed. Lithogenic bile is mainly caused by persistent hepatic hypersecretion of biliary cholesterol and sustained cholesterol-supersaturated bile is an essential prerequisite for the precipitation of solid cholesterol monohydrate crystals and the formation of cholesterol gallstones. The metabolic determinants of the supply of hepatic cholesterol molecules that are recruited for biliary secretion are dependent upon the input-output balance of cholesterol and its catabolism in the liver. The sources of cholesterol for hepatic secretion into bile have been extensively investigated; however, to what extent each cholesterol source contributes to hepatic secretion is still unclear both under normal physiological conditions and in the lithogenic state. Although it has been long known that biliary lithogenicity is initiated by hepatic cholesterol hypersecretion, the genetic mechanisms that cause supersaturated bile have not been defined yet. Identification of the Lith genes that determine hepatic cholesterol hypersecretion should provide novel insights into the primary genetic and pathophysiological defects for gallstone formation. In this review article, we focus mainly on the pathogenesis of the formation of supersaturated bile and gallstones from the viewpoint of genetics and pathophysiology. A better understanding of the molecular genetics and pathophysiology of the formation of cholesterol-supersaturated bile will undoubtedly facilitate the development of novel, effective, and noninvasive therapies for patients with gallstones, which would reduce the morbidity, mortality, and costs of health care associated with gallstones, a very prevalent liver disease worldwide.",
keywords = "Bile acid, Bile flow, Biliary secretion, Lith gene, Micelle, Vesicle",
author = "Wang, {Helen H.} and Tiangang Li and Piero Portincasa and Ford, {David A.} and Neuschwander-Tetri, {Brent A.} and Patrick Tso and Wang, {David Q.H.}",
year = "2017",
month = "6",
doi = "10.1016/j.livres.2017.05.005",
language = "English (US)",
volume = "1",
pages = "42--53",
journal = "Liver Research",
issn = "2542-5684",
number = "1",

}

TY - JOUR

T1 - New insights into the role of Lith genes in the formation of cholesterol-supersaturated bile

AU - Wang, Helen H.

AU - Li, Tiangang

AU - Portincasa, Piero

AU - Ford, David A.

AU - Neuschwander-Tetri, Brent A.

AU - Tso, Patrick

AU - Wang, David Q.H.

PY - 2017/6

Y1 - 2017/6

N2 - Cholesterol gallstone formation represents a failure of biliary cholesterol homeostasis in which the physical-chemical balance of cholesterol solubility in bile is disturbed. Lithogenic bile is mainly caused by persistent hepatic hypersecretion of biliary cholesterol and sustained cholesterol-supersaturated bile is an essential prerequisite for the precipitation of solid cholesterol monohydrate crystals and the formation of cholesterol gallstones. The metabolic determinants of the supply of hepatic cholesterol molecules that are recruited for biliary secretion are dependent upon the input-output balance of cholesterol and its catabolism in the liver. The sources of cholesterol for hepatic secretion into bile have been extensively investigated; however, to what extent each cholesterol source contributes to hepatic secretion is still unclear both under normal physiological conditions and in the lithogenic state. Although it has been long known that biliary lithogenicity is initiated by hepatic cholesterol hypersecretion, the genetic mechanisms that cause supersaturated bile have not been defined yet. Identification of the Lith genes that determine hepatic cholesterol hypersecretion should provide novel insights into the primary genetic and pathophysiological defects for gallstone formation. In this review article, we focus mainly on the pathogenesis of the formation of supersaturated bile and gallstones from the viewpoint of genetics and pathophysiology. A better understanding of the molecular genetics and pathophysiology of the formation of cholesterol-supersaturated bile will undoubtedly facilitate the development of novel, effective, and noninvasive therapies for patients with gallstones, which would reduce the morbidity, mortality, and costs of health care associated with gallstones, a very prevalent liver disease worldwide.

AB - Cholesterol gallstone formation represents a failure of biliary cholesterol homeostasis in which the physical-chemical balance of cholesterol solubility in bile is disturbed. Lithogenic bile is mainly caused by persistent hepatic hypersecretion of biliary cholesterol and sustained cholesterol-supersaturated bile is an essential prerequisite for the precipitation of solid cholesterol monohydrate crystals and the formation of cholesterol gallstones. The metabolic determinants of the supply of hepatic cholesterol molecules that are recruited for biliary secretion are dependent upon the input-output balance of cholesterol and its catabolism in the liver. The sources of cholesterol for hepatic secretion into bile have been extensively investigated; however, to what extent each cholesterol source contributes to hepatic secretion is still unclear both under normal physiological conditions and in the lithogenic state. Although it has been long known that biliary lithogenicity is initiated by hepatic cholesterol hypersecretion, the genetic mechanisms that cause supersaturated bile have not been defined yet. Identification of the Lith genes that determine hepatic cholesterol hypersecretion should provide novel insights into the primary genetic and pathophysiological defects for gallstone formation. In this review article, we focus mainly on the pathogenesis of the formation of supersaturated bile and gallstones from the viewpoint of genetics and pathophysiology. A better understanding of the molecular genetics and pathophysiology of the formation of cholesterol-supersaturated bile will undoubtedly facilitate the development of novel, effective, and noninvasive therapies for patients with gallstones, which would reduce the morbidity, mortality, and costs of health care associated with gallstones, a very prevalent liver disease worldwide.

KW - Bile acid

KW - Bile flow

KW - Biliary secretion

KW - Lith gene

KW - Micelle

KW - Vesicle

UR - http://www.scopus.com/inward/record.url?scp=85073764875&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85073764875&partnerID=8YFLogxK

U2 - 10.1016/j.livres.2017.05.005

DO - 10.1016/j.livres.2017.05.005

M3 - Review article

AN - SCOPUS:85073764875

VL - 1

SP - 42

EP - 53

JO - Liver Research

JF - Liver Research

SN - 2542-5684

IS - 1

ER -