Impaired biliary lipid secretion in obese Zucker rats: leptin promotes hepatic cholesterol clearance

• DOI: 10.1152/ajpgi.2001.281.2.g393
• Publication Date: 2017-12-24T15:33:10Z
• Authors: Sonya VanPatten; Narasimha Ranginani; Sarah Shefer; Lien B. Nguyen; Luciano Rossetti; David E. Cohen
• Keywords: Leptin receptor

Human obesity is associated with elevated plasma leptin levels. Obesity also an important risk factor for cholesterol gallstones, which form as a result of hypersecretion into bile. Because levels are correlated gallstone prevalence, we explored the effects acute administration on biliary secretion using lean ( FA/−) and obese fa/fa) Zucker rats. rats become hyperleptinemic due to homozygosity missense mutation in receptor, diminishes but does not completely eliminate responsiveness leptin. Rats were infused intravenously 12 h saline or pharmacological doses recombinant murine (5 μg · kg −1 min ) sufficient elevate concentrations 500 ng/ml compared basal 3 70 rats, respectively. was marked impairment secretion. In biles bile salt hydrophobicity decreased whereas phosphatidylcholine increased. High-dose partially normalized without altering lipid compositions, implying that both chronic relative resistance contributed impaired elimination. increased rates. Without affecting hepatic contents, downregulated activity 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, upregulated activities sterol 27-hydroxylase 7α-hydroxylase, lowered very low-density lipoprotein concentrations. Increased setting biosynthesis catabolism salts suggests promotes elimination cholesterol.