Increased rates of hepatic cholesterogenesis and fatty acid synthesis in septic rats in vivo: evidence for the possible involvement of insulin.
1. Sepsis induced by caecal ligation and puncture increased the rates of hepatic cholesterogenesis and fatty acid synthesis in vivo compared with sham-operated rats. These changes were accompanied by higher concentrations of lactate and pyruvate in blood and liver and an increase in plasma insulin. 2. The total activity of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.88) in liver was increased by sepsis, but there was no significant change in the expressed activity. Short-term insulin deficiency (induced by mannoheptulose or streptozotocin) decreased the rates of cholesterogenesis and fatty acid synthesis in livers of septic rats but did not alter the expressed/total activity of HMG-CoA reductase. 3. It is concluded that the increased rate of hepatic cholesterogenesis in septic rats is in part a result of the higher plasma insulin, the hormone acting to maintain the total activity of HMG-CoA reductase and to stimulate a step before the formation of HMG-CoA. 4. These changes may contribute to the hypertriacylglycerolaemia associated with sepsis.
de Vasconcelos
P R
PR
Nuffield Department of Clinical Medicine, Radcliffe Infirmary, Oxford, U.K.
Kettlewell
M G
MG
Gibbons
G F
GF
Williamson
D H
DH
D000818:Animals; D001424:Bacterial Infections / Q000378:metabolism*; D002784:Cholesterol / Q000096:biosynthesis*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007328:Insulin / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D005227:Fatty Acids; D007328:Insulin; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases