Abstract

Leptin and its receptor play several physiological roles in the canine gallbladder, and the dysregulation of leptin might play a role in the pathogenesis of gallbladder diseases such as gallbladder mucocele. Previous studies revealed a positive association between hyperlipidemia and gallstones in humans. However, the latter is still unclear in dogs with cholelithiasis. In this study, we examined the differences in leptin, leptin receptor, total cholesterol, and triglyceride levels between healthy dogs and dogs with cholelithiasis, and evaluated the correlation between leptin and hyperlipidemia. Twenty-eight healthy dogs and 34 client-owned dogs with cholelithiasis were enrolled in the study. Leptin concentrations and lipid profiles were determined from sera, and leptin and leptin receptor expression levels were quantified in gallbladder tissue. In dogs with cholelithiasis, serum concentrations of leptin (p < 0.001), total cholesterol (p < 0.001), and triglycerides (p < 0.001) were significantly higher compared with those in healthy dogs. Positive correlations were observed between serum leptin and total cholesterol (95% confidence interval (CI) = 0.61–0.89, r = 0.725, p < 0.001), and between leptin and triglycerides (95% CI = 0.63–0.89, r = 0.782, p < 0.001) in the cholelithiasis group. Hypercholesterolemia (Odds Ratio (OR) = 9.720; 95% CI = 1.148–82.318) and hypertriglyceridemia (OR = 12.913; 95% CI = 1.548–107.722) were shown to be risk factors for gallstone disease. In cholelithiasis patients who underwent cholecystectomy, serum leptin levels were significantly higher than in patients that had not undergone surgery (p < 0.001). Leptin and leptin receptor expression was upregulated in the gallbladder tissues of cholelithiasis patients (p < 0.01 and p < 0.001, respectively). These results indicate that increased serum leptin concentrations and hyperlipidemia (hypercholesterolemia or hypertriglyceridemia) are associated with canine cholelithiasis and that homeostatic imbalance of these parameters might affect the pathogenesis of gallstones.

Highlights

  • Cholelithiasis is a pathological condition in which choleliths are found within the gallbladder or intrahepatic or extrahepatic ductal system [1]

  • Leptin and leptin receptor expression was upregulated in the gallbladder tissues of cholelithiasis patients (p < 0.01 and p < 0.001, respectively). These results indicate that increased serum leptin concentrations and hyperlipidemia are associated with canine cholelithiasis and that homeostatic imbalance of these parameters might affect the pathogenesis of gallstones

  • To evaluate the differences in leptin and insulin concentrations in the cholelithiasis patients with or without Diabetes mellitus (DM), the members of the cholelithiasis group were separated into dogs with DM and without it, and we showed that the concurrence of DM with cholelithiasis did not significantly affect serum leptin and insulin levels (p = 0.717 and p = 0.089, respectively; Fig 3)

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Summary

Introduction

Cholelithiasis is a pathological condition in which choleliths are found within the gallbladder or intrahepatic or extrahepatic ductal system [1]. Cholelithiasis is one of the major causes of a life-threatening biliary tract disease, such as extrahepatic biliary tract obstruction caused by the migration of one or more choleliths into the common bile duct, and it may be related to the occurrence of cholecystitis and pancreatitis [2, 3]. Whereas dietary-induced cholesterol gallstones are common in humans, canine choleliths are primarily composed of calcium bilirubinate with cholesterol and bilirubin [1, 2]. The exact etiopathogenesis of cholelithiasis in dogs is unclear, based on studies in humans and experimental animals, it has been suggested that decreased gallbladder motility, excess secretion of mucin, and altered absorption/secretion of the gallbladder are involved in the pathogenesis [4,5,6,7,8]

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