Diabetes and hyperlipidemia correlate with gallbladder contractility in leptin-related murine obesity

Resistin-Like Molecule Alpha Reduces Gallbladder Optimal Tension

“…Previous studies from our laboratory have demonstrated that Lep ob and Lep db mice have hyperglycemia, insulin-resistance, hyperinsulinemia, hyperlipidemia, enlarged gallbladders, and reduced response of their gallbladder smooth muscle to neurotransmitters such as ACh, NPY, and CCK. [6][7][8][9]21,22 The serum glucose, insulin, cholesterol, and triglycerides in these mice correlated inversely with their in vitro gallbladder responses. 6 We have also shown that the lipids in the gallbladder wall of lean (C57BL/6J) and obese (Lep ob ) mice correlate with the impaired in vitro gallbladder response to neurotransmitters.…”

“…[6][7][8][9]21,22 The serum glucose, insulin, cholesterol, and triglycerides in these mice correlated inversely with their in vitro gallbladder responses. 6 We have also shown that the lipids in the gallbladder wall of lean (C57BL/6J) and obese (Lep ob ) mice correlate with the impaired in vitro gallbladder response to neurotransmitters. 23 These findings suggest that insulin resistance and/or fat infiltration mediate the gallbladder dysmotility in these diabetic obese mice.…”

“…[3][4][5] Recent animal and human data from our laboratory suggest that insulin resistance is associated with increased gallbladder volume and/or impaired gallbladder emptying. [6][7][8][9][10] In addition, gallbladders of diabetic patients have been shown to be enlarged with decreased emptying in response to a meal. 3,11 Resistin is a member of a family of resistin-like molecules (RELMs), which were earlier discovered as the FIZZ gene family.…”

Cholecystosteatosis: an Explanation for Increased Cholecystectomy Rates

“…gallbladder response correlates inversely with serum glucose, insulin, cholesterol, and triglycerides. 31 In addition, we have demonstrated that administration of leptin to leptin-deficient mice restores gallbladder contractility, decreases gallbladder dry weight, 32 and decreased the gene expression of enzymes responsible for lipid metabolism including fatty acid synthase, HMG Co A reductase, and diacylglycerol acyltransferase (unpublished data). More recently, we have shown that lean mice fed a high fat diet have increased gallbladder wall cholesterol and cholesterol/phospholipid ratio compared to lean mice fed a low fat chow diet.…”

“…Early studies from this and other laboratories suggested that decreased gallbladder emptying and abnormal gallbladder absorption were early events in gallstone pathogenesis. 49,50 More recent studies have suggested that increased insulin resistance and hyperlipidemia also are associated with altered gallbladder volume and motility, 23,31 factors that may lead to biliary pain. A recent murine study from this laboratory suggested that diet-induced and congenital obesity are associated with increased gallbladder wall fat and poor gallbladder emptying.…”