Lipogenesis from ketone bodies in perfused livers from streptozocin-induced diabetic rats.
Production of ketone bodies and their contribution to lipogenesis were measured in isolated livers from normal and streptozocin-induced diabetic (STZ-D) rats perfused with tracer amounts of 3H2O and (R)-3-hydroxy[3-14C]butyrate. Diabetes decreased by 80-95% the total rates of fatty acid and 3-beta-hydroxysterol synthesis in perfused livers and livers of live rats. The activity of cytosolic acetoacetyl-CoA synthetase was slightly (17%) decreased in livers from STZ-D rats. The incorporation of ketone bodies into fatty acids and sterols was markedly inhibited in perfused livers from STZ-D rats despite the stimulation of ketogenesis by diabetes and the presence of oleate. Treatment of the rats with insulin before liver perfusion led to a normalization of the rates of ketogenesis and fatty acid synthesis. The rates of sterol synthesis were only partially normalized by insulin treatment. We conclude that in STZ-D, ketosis does not stimulate hepatic lipogenesis via cytosolic activation of acetoacetate.
Freed
L E
LE
Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge.
Endemann
G
G
Tomera
J F
JF
Gavino
V C
VC
Brunengraber
H
H
D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000378:metabolism; D000818:Animals; D003066:Coenzyme A Ligases / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005227:Fatty Acids / Q000096:biosynthesis; D006885:Hydroxybutyrates / Q000378:metabolism; D007657:Ketone Bodies / Q000378:metabolism*; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013261:Sterols / Q000096:biosynthesis
D000090:Acetoacetates; D005227:Fatty Acids; D006885:Hydroxybutyrates; D007657:Ketone Bodies; D008055:Lipids; D013261:Sterols; C016635:acetoacetic acid; D003066:Coenzyme A Ligases; C023747:acetoacetyl-CoA synthetase; D020155:3-Hydroxybutyric Acid