Relationship between lipogenesis, ketogenesis, and malonyl-CoA content in isolated hepatocytes from the obese Zucker rat adapted to a high-fat diet.
The relationship between lipogenesis and ketogenesis and the concentration of malonyl coenzyme A (CoA) was investigated in hepatocytes from adult obese Zucker rats and their lean littermates fed either a control low-fat diet or a high-fat diet (30% lard in weight). With the control diet, lipogenesis--although strongly inhibited in the presence of either 1 mmol/L oleate, 10(-6) mol/L glucagon or 0.1 mmol/L TOFA (a hypolipidemic drug)--remained about fifteen-fold higher in the obese rats than in the lean rats. In contrast, ketogenesis under some conditions (oleate + TOFA) was not significantly lower (30%) as compared with the lean rats. After adaptation to the high-fat diet, lipogenesis was depressed fourfold in the lean rats and ninefold in the obese ones; however its magnitude remained significantly higher in the latter, namely at a value close to that measured in control-fed lean rats. Ketogenesis was comparable in lean and obese rats and much higher in the presence of 1 mmol/L oleate than of 0.3 mmol/L oleate, whereas lipogenesis did not vary with increasing oleate concentration in the medium. Acetyl-CoA carboxylase activity measured in liver homogenates was higher in the obese group, but was stepwise inhibited by increasing concentrations of oleyl-CoA regardless of the diet for both lean and obese rats, thus showing no abnormality of in vitro responsiveness to this inhibitor. With the control diet, hepatocyte malonyl-CoA levels were significantly higher in the obese rats, both in the basal state and after inhibition of lipogenesis by oleate and TOFA.(ABSTRACT TRUNCATED AT 250 WORDS)
Malewiak
M I
MI
Griglio
S
S
Le Liepvre
X
X
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D004041:Dietary Fats / Q000378:metabolism*; D005934:Glucagon / Q000378:metabolism; D066298:In Vitro Techniques; D007657:Ketone Bodies / Q000096:biosynthesis*; D007773:Lactates / Q000378:metabolism; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker
D000214:Acyl Coenzyme A; D004041:Dietary Fats; D007657:Ketone Bodies; D007773:Lactates; D008055:Lipids; D009829:Oleic Acids; D011773:Pyruvates; D019301:Oleic Acid; D008316:Malonyl Coenzyme A; D005934:Glucagon; D000103:Acetyl-CoA Carboxylase