Stimulation of cholesterol synthesis and hepatic lipogenesis in patients with severe malabsorption

Abstract

Patients with severe malabsorption have abnormal lipid metabolism with low plasma cholesterol and frequently high triglyceride (TG) levels. The mechanisms behind these abnormalities and the respective roles of malabsorption itself and of the parenteral nutrition given to these patients are unclear. We measured endogenous lipids synthesis (cholesterol synthesis and hepatic lipogenesis) and the expression (mRNA concentrations in circulating mononuclear cells) of regulatory genes of cholesterol metabolism in 10 control subjects and 22 patients with severe malabsorption receiving (n = 18) or weaned of parenteral nutrition (n = 4). Patients had low plasma cholesterol (P lt; 0.01) and raised TG (P < 0.05) levels. Both fractional and absolute cholesterol synthesis (P < 0.001) and hepatic lipogenesis (P < 0.01) were increased. These abnormalities are independent of parenteral nutrition since they were present in patients receiving or weaned of parenteral nutrition. No relation between hepatic lipogenesis and plasma TG levels was found, suggesting that other metabolic abnormalities participated in hypertriglyceridemia. HMG-CoA reductase and LDL receptor mRNA levels were decreased (P < 0.05) in patients on long-term parenteral nutrition. HMG-CoA reductase mRNAs were normal in weaned patients. Severe malabsorption induces large increases of cholesterol synthesis and hepatic lipogenesis independently of the presence of parenteral nutrition. These abnormalities are probably due to the malabsorption of bile acids.