(6_ 14 C) glucose (1.5-2 gm/kg body weight) was administered orally to fasted rats fed for five weeks from weaning a fat or a carbohydrate synthetic diet. Rats were killed by deca-PAtation at 30, 60, 120 and 180 minutes after the load. ein the gut, glucose (6-14 C) glucose and insulin in the serum, glycogen and (1~C) glycogen in the liver, were measured. Fat-adapted rats exhibited impaired glucose tolerance and sensitivity to endogenous insulin which resulted in higher levels of exogenous glucose in the serum and in some slackening of disposal of the load by the tissues. An altered r~ lease of glucose by the liver does not seem to be a major factor of hyperglycaemia in these conditions. The level of liver glycogen before the load and throughout the experiment is higher in the fat group. As in the contral group, hepatic glycogen synthesis after glucose administration develops linearly between 30 and 120 minutes without any evident relation to the time variation of the level and the specific radioactivity of serum glucose. In addition, the specific activity of glycogen stabilized to a value much low• er than that of the load glucose. After fat diet, a significant reduction of the amount of 14 carbon incorporated into liver glycogen was observed which can contribute to the decrease of tolerance to orally administered glucose.

Epididymal adipose tissue of rats fed a high-fat diet and submitted or not to a 24-h fast before the experiment, was incubated with 10 mM glucose labelled with 14C at C-6, C-1 or universally, in the presence of insulin (1000 yU/ml). The results were used to estimate the glucose carbon flow through the various metabolic pathways and to establish a balance of production and utilization of reducing equivalents in the cytoplasmic compartment.Although previously altered by the fat diet, glucose metabolism is shown to be still highly sensitive to the effect of fasting which mostly results in a further reduction of fatty acid synthesis and in a further increase of glucose conversion into lactate. This effect is rather parallel to the known effect of fasting on glucose metabolism in adipose tissue of rats fed a normal fat-poor diet.In adipose tissue of rats fed a fat diet, the lactate/pyruvate ratio reaches an abnormally high value which is consistent with a calculated excess of production over utilization of reducing equivalents. A 24-h fast induces a drop of the lactate/pyruvate ratio together with a significant improvement of the balance between production and utilization. Thus, this effect is quite in opposition with the slight increase in the NADH : NAD' ratio currently observed in adipose tissue of fasted rats after a normal fat-poor diet.It can be concluded from the results of this work that the cytoplasmic redox potential is not a major factor in the control of glucose metabolism in adipose tissue.

Rats were fed for 3-4 weeks from weaning either a control carbohydrate diet (5801, starch) or one of two fat diets (35.5O/, and 58O/, lard); some rats were changed from fat (35.5O/,) to control diet 1 to 5 days before the experiment.Epididymal adipose tissue was incubated in the presence of [U-14C]glucose (10 mM) and (or no) insulin (100 pU/ml). Glucose uptake and conversion into CO,, glycogen, fatty acid and glyceride-glycerol were measured together with lactate and glycerol release during a 2-hour incubation. The level of free fatty acids in tissue was also determined.Incorporations of glucose carbon into CO, and fatty acid were severely reduced by both fat diets and increased during the first 5 days after change to control diet in an almost linear way, to values still far from the control values. After both fat diets, lactate release was doubled, accounting for half the glucose uptake. Lipolysis, measured by glycerol release, was unchanged (35.501, fat) or increased (58OlO fat) by fat diet, but the antilipolytic effect of insulin was entirely preserved in both fat conditions.A 6-hour preincubation of the tissue with glucose increased glucose uptake and metabolism in adipose tissue of control and fat-fed rats, independently of the presence of insulin (50 pU/ml) in the medium. This effect does not seen to have any relation with the progressive restoration of lipogenesis observed after changing the animals from fat to carbohydrate diet.I n a previous work [l], a fat-rich, carbohydratepoor diet has been shown to induce in the rat high levels of serum glucose, indicating a disturbed regulation of glycaemia. After a glucose load, the peripheral utilization of administered glucose and the sensitivity to endogeneous insulin were found to be reduced while glucose production and glycogen synthesis in the liver did not seem much altered [2].I n the same nutritional conditions, a decrease of glucose metabolism in vitro waa reported in diaphragm muscle and shown to be directly related to high oxidation of fatty acid [3].I n adipose tissue, fat diet is known to lower markedly glucose metaoblism in vitro in the mouse [5] and rat [6-91 and to alter the activities of some enzymes involved in lipogenesis [lo, 111. Moreover, long-term fat feeding results in excessive accumulation of fat and in a typical state of experimental obesity [ 12 -141.The present work was undertaken to provide more complete information about the impaired metabolism of glucose and lipid in adipose tissue after fat diet.Enzymes.

Adipose tissue of rats fed from weaning a fat diet or a control carbohydrate diet, was incubated with [U‐14C]glucose or [6‐14C]glucose (20 mM) or with unlabelled glucose (20 mM) and trace amount of [U‐14C]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 14C with CO2, accounting for up to 35% of the total 14CO2 production from [U‐14C]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.