Faculty Collaboration Database

Leptin-resistant obese mice do not form biliary crystals on a high cholesterol diet. J Surg Res 2004 Dec;122(2):145-9

Date

11/24/2004

Pubmed ID

15555610

DOI

10.1016/j.jss.2004.04.012

Scopus ID

2-s2.0-8844280976 (requires institutional sign-in at Scopus site)   10 Citations

Abstract

INTRODUCTION: 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.

Author List

Graewin SJ, Lee KH, Tran KQ, Goldblatt MI, Svatek CL, Nakeeb A, Pitt HA

Author

Matthew I. Goldblatt MD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Body Weight
Cholelithiasis
Cholesterol
Cholesterol, Dietary
Crystallization
Dose-Response Relationship, Drug
Drug Resistance
Female
Gallbladder
Leptin
Liver
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Obesity