Studies on the Metabolic Effect Induced in the Rat by a High‐Fat Diet

Adipose tissue of rats fed from weaning a fat diet or a control carbohydrate diet, was incubated with [U‐ 14 C]glucose or [6‐ 14 C]glucose (20 mM) or with unlabelled glucose (20 mM) and trace amount of [U‐ 14 C]pyruvate, in the presence of insulin (1000 μU/ml). Fluxes of carbon through various metabolic pathways were calculated. In adipose tissue of fat‐fed rats, the rate of glucose carbon flow at the level of pyruvate decarboxylation and in fatty acid synthesis from acetyl‐CoA, was reduced to 5% or less of the control. The rate of glycolysis was only decreased to 20% while the greatest part of intermediary pyruvate was diverted into lactate. Recycling of pyruvate through a partial reversal of glycolysis was also demonstrated and was concomitant with an exchange of 14 C with CO 2 , accounting for up to 35% of the total 14 CO 2 production from [U‐ 14 C]glucose. A balance of production and utilization of reduced nucleotide coenzymes in the cytoplasm during glucose metabolism was established. In contrast with the control tissue, a net excess was obtained in adipose tissue of fat‐fed rats. Alteration of the cytoplasmic redox state was also indicated by an abnormally high lactate/pyruvate ratio. Several aspects of the glucose metabolism show the existence of a high energetic level or ATP:ADP ratio. The significance of the findings is discussed with regard to the control of lipogenesis in adipose tissue.