Cholesterol metabolism: regulatory effects of the vagus in the normal and diabetic animal.

: The activities of beta-Hydroxy-beta-methylglutaryl CoA reductase (HMG CoA reductase), Acyl CoA: Cholesterol-O-acyltransferase (ACAT) and cholesterol 7 alpha-hydroxylase, the major enzymes involved in cholesterol metabolism, were determined in diabetic and non-diabetic rats after vagotomy and compared with those of sham-operated controls. Hepatic cholesterol levels and serum lipid profiles were also examined. In the non-diabetic animals vagotomy produced a significant increase in HMG CoA reductase (the rate limiting enzyme of cholesterol biosynthesis), and ACAT (the enzyme responsible for intracellular esterification) activities, while the activity of cholesterol 7 alpha-hydroxylase (which catalyses the rate determining step of bile acid biosynthesis) was significantly decreased. These rats had higher levels of free and esterified cholesterol in the liver and serum cholesterol levels were also increased in comparison with sham-operated animals. Vagotomized diabetic rats had similar HMG CoA reductase activity, but significantly reduced ACAT and reduced cholesterol 7 alpha-hydroxylase activity in comparison with sham-operated diabetic rats. There were significant alterations in hepatic and serum cholesterol fractions in both normal and diabetic rats after vagotomy. The results suggest that vagotomy leads to an increased rate of cholesterol synthesis and a decreased rate of cholesterol utilization, thus providing a possible mechanism for excessive cholesterol accumulation. These results are discussed in relation to alterations in cholesterol metabolism found in diabetic autonomic neuropathy.