Biliary lipids and cholesterol gallstone disease

David Q.H. Wang, David E. Cohen, Martin C. Carey

Research output: Contribution to journalReview article

121 Citations (Scopus)

Abstract

Biliary lipids are a family of four dissimilar molecular species consisting of a mixture of bile salts (substituted cholanoic acids), phospholipids, mostly (>96%) diacylphosphatidylcholines, unesterified cholesterol, and bilirubin conjugates known trivially as lipopigments. The primary pathophysiological defect in cholesterol gallstone disease is hypersecretion of hepatic cholesterol into bile with less frequent hyposecretion of bile salts and/or phospholipids. Several other gallbladder abnormalities contribute and include hypomotility, immune-mediated inflammation, hypersecretion of gelling mucins, and accelerated phase transitions; there is also reduced intestinal motility that augments "secondary" bile salt synthesis by the anaerobic microflora. Cholesterol nucleation is initiated when unilamellar vesicles of cholesterol plus biliary phospholipids fuse to form multilamellar vesicles. From these "plate-like" cholesterol monohydrate crystals, the building blocks of macroscopic stones are nucleated heterogeneously by mucin gel. Multiple Lith gene loci have been identified in inbred mice, paving the way for discovery of an ever-increasing number of LITH genes in humans. Because of the frequency of the metabolic syndrome today, insulin resistance and LITH genes all interact with a number of environmental cholelithogenic factors to cause the gallstone phenotype. This review summarizes current concepts of the physical-chemical state of biliary lipids in health and in lithogenic bile and outlines the molecular, genetic, hepatic, and cholecystic factors that underlie the pathogenesis of cholesterol gallstones.

Original languageEnglish (US)
JournalJournal of Lipid Research
Volume50
Issue numberSUPPL.
DOIs
StatePublished - Apr 1 2009
Externally publishedYes

Fingerprint

Gallstones
Cholesterol
Lipids
Bile Acids and Salts
Phospholipids
Genes
Mucins
Gallbladder
Bile
Chemical Phenomena
Physical Phenomena
Unilamellar Liposomes
Gastrointestinal Motility
Liver
Phase Transition
Electric fuses
Bilirubin
Insulin Resistance
Molecular Biology
Nucleation

Keywords

  • Bile flow
  • Bile salt
  • Biliary lipid secretion
  • Cholesterol
  • Crystallization
  • Hydrophilic-hydrophobic balance
  • Lipid transporter
  • Liquid crystal
  • LITH gene
  • Micelle
  • Mucin
  • Nucleation
  • Phase diagram
  • Phospholipid
  • Vesicle

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Biliary lipids and cholesterol gallstone disease. / Wang, David Q.H.; Cohen, David E.; Carey, Martin C.

In: Journal of Lipid Research, Vol. 50, No. SUPPL., 01.04.2009.

Research output: Contribution to journalReview article

Wang, David Q.H. ; Cohen, David E. ; Carey, Martin C. / Biliary lipids and cholesterol gallstone disease. In: Journal of Lipid Research. 2009 ; Vol. 50, No. SUPPL.
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