Diabetes and hyperlipidemia correlate with gallbladder contractility in leptin-related murine obesity.
Obesity is associated with many comorbid conditions including diabetes, hyperlipidemia, and gallstones. However, the interaction among these modalities remains unclear. We recently demonstrated that both leptin-deficient and leptin-resistant obese mice have impaired biliary motility. These obese mice also are diabetic and hyperlipidemic. Therefore, we tested the hypothesis that serum glucose, insulin, cholesterol, and triglyceride levels would correlate with gallbladder contractility. Thirty-four lean control, 10 lean heterozygous leptin-deficient, 18 obese homozygous leptin-deficient, and 12 obese homozygous leptin-resistant mice were fed a nonlithogenic chow diet while nine lean control and nine obese homozygous leptin-deficient mice were fed a high-cholesterol diet for 4 weeks. In vitro gallbladder responses to cholecystokinin (CCK; 10(-8) mol/L), acetylcholine (ACh; 10(-5) mol/L), and neuropeptide Y (NPY; 10(-6) mol/L) were measured. Serum glucose, insulin, cholesterol, and triglyceride levels were measured from pooled serum from an additional 704 animals. Gallbladder responses were greatest for CCK, intermediate for ACh, and least for NPY. Serum glucose, insulin, cholesterol, and triglyceride levels and body weight all correlated similarly, negatively, and significantly (P<0.001) with gallbladder contractility. Hyperglycemia, insulin-resistance, hyperlipidemia, and body weight in obese mice with leptin dysfunction are associated with poor gallbladder contractility, which in turn may contribute to the association between obesity and gallstone formation.
Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Khoi Q
KQ
Tran
Matthew I
MI
Goldblatt
Deborah A
DA
Swartz-Basile
Carol
C
Svatek
Attila
A
Nakeeb
Henry A
HA
Pitt
D000818:Animals; D001786:Blood Glucose; D002784:Cholesterol / Q000097:blood; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000097:blood / Q000503:physiopathology*; D016473:Gallbladder Emptying / Q000502:physiology*; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000502:physiology*; D051379:Mice; D009765:Obesity; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D014280:Triglycerides; D002784:Cholesterol