The activity and mRNA concentrations of two lipogenic enzymes, fatty-acid synthase and acetylCoA carboxylase were measured in the liver and white adipose tissue of rats weaned to a carbohydraterich diet containing either long-chain or medium-chain fatty acids, and compared to those of rats weaned on a diet containing less than 1% (total energy) fat (high-carbohydrate diet). In the liver, the diet containing long-chain fatty acids inhibited the increase of both lipogenic-enzyme mRNA concentrations and activities seen at weaning on the high-carbohydrate diet but did not prevent the decrease in phosphoenolpyruvate carboxykinase mRNA and activity. In contrast, the diet containing medium-chain fatty acids induced a slower but finally similar increase in lipogenic-enzyme mRNA concentrations and activities. In adipose tissue, a similar trend was observed, although the inhibitory effect of the diet containing long-chain fatty acids was considerably less marked than in liver. It is concluded that medium-chain and long-chain fatty acids have not the same inhibitory potency of the gene expression of lipogenic enzymes, and that long-chain fatty acids have a more marked effect in the liver.

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In cultured adipose tissue of suckling rats, glucose alone is able to induce the appearance of fatty-acid synthase and acetyl-CoA carboxylase mRNA by a mechanism involving glucose-6-phosphate accumulation; insulin alone has no effect but potentiates the effect of glucose. In the present study, we have analysed in cultured adipose tissue the effects of other hormones on the expression of these enzymes as well as on phosphoenolpyruvate carboxykinase. Triiodothyronine has only a marginal effect on fatty-acid synthase expression, in the absence or presence of glucose and insulin. A synthetic glucocorticoid, dexamethasone, opposes the inductive effect of glucose and insulin on fatty-acid synthase expression but increases the expression of phosphoenolpymvate carboxykinase. A P-agonist, isoproterenol totally inhibits the inductive effect of glucose and insulin on acetyl-CoA carboxylase and fatty-acid synthase expression whereas it increases the expression of phosphoenolpyruvate carboxykinase. Similarly, glucagon and cAMP have antagonistic effects on glucose and insulin-induced fatty-acid synthase expression. These inhibitory effects cannot be explained only by a reduction in glucose-6-phosphate concentration. We conclude that, in adipose tissue, dexamethasone and CAMP-generating hormones are negative regulators of lipogenic enzyme expression. Finally, the regulation of phosphoenolpyruvate carboxykinase expression in adipose tissue is similar to that found in the liver, i.e. inhibition by insulin and glucose and activation by glucocorticoids and CAMP.The main enzymes regulating the rate of fatty acid synthesis are acetyl-CoA carboxylase (ACC) that catalyses the synthesis of malonyl-CoA and fatty-acid synthase (FAS), a multifunctional protein that synthesizes fatty acids by adding malonyl-CoA units to an acetyl-CoA primer. We have shown that glucose alone was able to stimulate the expression of FAS and ACC in cultured white adipose tissue of suckling rats [I]. Insulin alone has no effect on FAS and ACC expression but potentiates the effect of glucose. Finally, it was suggested that glucose 6-phosphate could be the intracellular metabolite involved in the stimulation of lipogenic enzyme gene expression in response to glucose and insulin.Other hormones than insulin could be implicated in the control of lipogenic enzyme expression in adipose tissue. Indeed, in the liver of adult rat, FAS and ACC activities and mRNA were increased by thyroid hormones [2-61. In cultured hepatocytes from chick embryos [7, 81 and [9], 3,5,3'-triiodothyronine increased the rate of transcription and mRNA concentration of FAS and ACC. It has also been reported that thyroid hormones and dietary carbohydrates acted synergistically in the regulation of liver FAS [4]. Glucagon and cAMP decreased the activities of FAS and ACC in fed rats [lo] and the expression of FAS in the liver of mouse [ l l ] and in cultured hepatocytes from chick embryo [7, 121. The role of glucocorticoids on lipogenic enzyme gene expression is unclear in the liver. In a recen...

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Acarbose is a potent intestinal glucosidase inhibitor which could have an anti-obesity property by reducing postprandial plasma glucose and insulin levels, potentially responsible for high rates of lipid synthesis in adipose tissue. We have tested this hypothesis by studying rats during the weaning period, when the lipogenic capacity of the adipose tissue develops. Rats were treated from age 19 days onwards with acarbose (10 mg/100 g diet) and studied at age 30 days. Acarbose was efficient in reducing postprandial excursions of both blood glucose and plasma insulin. Acarbose-treated rats behave like rats continuously infused with glucose with no metabolic signs of carbohydrate deprivation since gluconeogenesis was not activated. There was no massive caecal fermentation of carbohydrate since volatile fatty acids did not significantly increase in the portal blood. One of the most striking features of the acarbose-treated rats was the reduction of adipose tissue weight due to a reduced adipocyte size. This was concomitant with a reduced lipogenic capacity from glucose in isolated adipocytes under insulin stimulation. The activity of fatty acid synthase and acetyl-CoA carboxylase was decreased concomitantly with a reduced expression of their specific mRNA. This study allows the conclusion that postprandial hyperinsulinaemia and hyperglycaemia have a major role in the control of expression of lipogenic enzymes and thus on adipose tissue lipogenic capacity.