title: Leptin-resistant obese mice do not form biliary crystals on a high cholesterol diet.
abstract: BACKGROUND
  Human obesity is associated with leptin resistance and cholesterol gallstone formation. Previously, we demonstrated that leptin-resistant (Lep(db)) obese mice fed a low cholesterol diet have enlarged gallbladders, but a decreased cholesterol saturation index, despite elevated serum cholesterol. Obese humans, however, consume a high cholesterol diet. Therefore, we hypothesized that on a high cholesterol diet, leptin-resistant mice would have cholesterol saturated bile and would form biliary crystals.
  
  
  METHODS
  Eight-week old female lean control (n = 70) and leptin-resistant (n = 72) mice were fed a 1% cholesterol diet for 4 weeks. All animals then had cholecystectomies. Bile was collected, grouped into pools to determine cholesterol saturation index (CSI), and examined for cholesterol crystals. Serum cholesterol and leptin were also measured.
  
  
  RESULTS
  Gallbladder volumes for Lep(db) mice were enlarged compared with the lean mice (35.8 microl versus 19.1 microl, P < 0.001), but the CSI for the Lep(db) mice was lower than for the lean animals (0.91 versus 1.15, P < 0.03). The obese animals did not form cholesterol crystals, whereas the lean animals averaged 2.2 crystals per high-powered field (hpf) (P < 0.001). Serum cholesterol and leptin were also elevated (P < 0.001) in the obese animals.
  
  
  CONCLUSIONS
  These data suggest that Lep(db) obese mice fed a high cholesterol diet have increased gallbladder volume and decreased biliary cholesterol saturation and crystal formation despite elevated serum cholesterol compared with lean control mice. We conclude that the link among obesity, diet, and gallstone formation may not require hypersecretion of biliary cholesterol and may be related to the effects of diabetes, hyperlipidemia, or both on gallbladder motility.
authors.affiliation: Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Shannon J
authors.initials: SJ
authors.lastname: Graewin
authors.forename: Keun-Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Khoi Q
authors.initials: KQ
authors.lastname: Tran
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Goldblatt
authors.forename: Carol L
authors.initials: CL
authors.lastname: Svatek
authors.forename: Attila
authors.initials: A
authors.lastname: Nakeeb
authors.forename: Henry A
authors.initials: HA
authors.lastname: Pitt
mesh_terms: D000818:Animals; D001835:Body Weight; D002769:Cholelithiasis / Q000209:etiology*; D002784:Cholesterol; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D003460:Crystallization; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005704:Gallbladder / Q000473:pathology; D020738:Leptin / Q000378:metabolism*; D008099:Liver / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*
chemical_list: D002791:Cholesterol, Dietary; D020738:Leptin; D002784:Cholesterol