Hepatobiliary Diseases and Insulin Resistance

Abstract

In recent years, there has been an increasing prevalence of obesity and related diseases. This epidemiological change has increased the interest of researchers in the molecular and biochemical pathways involved in the pathogenesis of hepatic and biliary diseases. Insulin resistance is considered the major mechanism involved in the hepatic and biliary manifestations of obesity. Epidemiological, clinical, and basic research demonstrates that insulin resistance is associated with gallstone disease, nonalcoholic fatty liver disease, and poor outcomes in viral hepatitis C treatments. Fascinating experimental evidence demonstrates that fat-induced hepatic insulin resistance may result from the activation of kinases leading to impaired insulin signaling. The insulin-resistant state is characterized by a failure to suppress hepatic glucose production and glycogenolysis, with enhanced fat accumulation in hepatocytes because of increased lipolysis, increased free fatty acid uptake by hepatocytes, and increased hepatic synthesis of triglycerides. This molecular signaling induces a low-grade chronic inflammatory state, characterized by increased levels of proinflammatory molecules and acute-phase proteins. This review summarizes the most important molecular and biochemical issues in the hepatic and biliary diseases associated with insulin resistance.

Dietary extra-virgin olive oil rich in phenolic antioxidants and the aging process: long-term effects in the rat

“…Also, liver steatosis was more pronounced in the olive oil-treated animals, as indicated by the increase in organ weight and triglyceride content. An increase in the hepatic synthesis and production of triglycerides is frequently associated with insulin resistance and obesity in humans [32]. The olive oil-fed animals also showed insulin resistance in adipose tissue, at variance with those fed corn oil, and a tendency towards increased insulin plasma levels.…”

Gallbladder and gastric motility in obese newborns, pre‐adolescents and adults

“…[35][36][37] In a recent study, a prevalence of gallstones of 2% was found by ultrasound in asymptomatic obese children and adolescents between 8 and 18 years of age (eight girls and two boys over 493 subjects), all of whom were postpubertal. 6 The link between obesity and the risk of gallbladder disease seems to be secondary, at least in part, to insulin resistance, 38 a mechanism also most likely involving increased serum levels of leptin 39 and increased hepatic secretion of cholesterol. 8 Our results found the presence of a distinctive gallbladder hypomotility in adult obese.…”

Sonographic Evaluation of Gallbladder Motility in Children with Chronic Functional Constipation

“…In a recent study by Di Ciaula et al ., 32 the authors demonstrated gallbladder and gastric motility defects were associated with obesity in preadolescents and adults. The link between obesity and the risk of gallbladder disease seems to be secondary, at least in part, to insulin resistance, 33 a mechanism also most likely involving increased serum levels of leptin 34 and increased hepatic secretion of cholesterol.…”