title: Leptin-resistant obese mice have paradoxically low biliary cholesterol saturation.
abstract: BACKGROUND
  Human obesity is associated with leptin resistance, elevated serum glucose and lipids, hepatic steatosis, and cholesterol gallstone formation. These gallstones are thought to result from hypersecretion of biliary cholesterol as well as biliary stasis. Leptin-resistant Lep(db) obese mice, which are known to have elevated serum leptin, glucose, and lipids, as well as hepatic steatosis, should be an appropriate model for human gallstone formation. Therefore, we tested the hypothesis that leptin-resistant mice would have increased gallbladder volume, biliary cholesterol saturation, and cholesterol crystal formation.
  
  
  METHODS
  Sixty lean control mice and 60 Lep(db) obese mice on a low cholesterol chow diet were studied. Gallbladder volumes were measured and bile was pooled to calculate cholesterol saturation index. Serum cholesterol, glucose, and leptin levels were determined from pooled serum. Hepatic fat vacuoles were counted. Bile from a second group of 90 lean control and 59 obese mice was observed microscopically for cholesterol crystal formation.
  
  
  RESULTS
  Leptin-resistant obese mice have significantly higher serum cholesterol, glucose, and leptin levels, hepatic fat vacuoles, and gallbladder volume than lean control mice. However, biliary cholesterol saturation index and cholesterol crystal formation were significantly diminished in the obese mice.
  
  
  CONCLUSIONS
  These data suggest that leptin-resistant Lep(db) obese mice have (1) increased gallbladder volume, (2) decreased biliary cholesterol saturation despite elevated serum cholesterol and hepatic steatosis, and (3) decreased in vitro cholesterol crystal formation. We conclude that the link between obesity and gallstone formation does not require hypersecretion of biliary cholesterol.
authors.affiliation: Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA
authors.forename: Khoi Q
authors.initials: KQ
authors.lastname: Tran
authors.forename: Shannon J
authors.initials: SJ
authors.lastname: Graewin
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Swartz-Basile
authors.forename: Attila
authors.initials: A
authors.lastname: Nakeeb
authors.forename: Carol L
authors.initials: CL
authors.lastname: Svatek
authors.forename: Henry A
authors.initials: HA
authors.lastname: Pitt
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism*; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D003460:Crystallization; D004351:Drug Resistance; D005260:Female; D005704:Gallbladder / Q000473:pathology; D020738:Leptin / Q000097:blood / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009929:Organ Size; D014617:Vacuoles / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D001786:Blood Glucose; D020738:Leptin; D002784:Cholesterol