Summary
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 of postprandial hyperinsulinaemia and hyperglycaemia have a major role in the control of expression of lipogenic enzymes and thus on adipose tissue lipogenic capacity.
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References
Caspary WF (1978) Sucrose malabsorption in man after ingestion of α-glucoside hydrolase inhibitor. Lancet I:1231–1233
Puls W, Keup U, Krause HP et al. (1980) Pharmacology of a glucosidase inhibitor. Front Hormone Res 7:235–247
Puls W, Bishoff H (1983) Pharmacology of amylase and glucosidase-inhibitors. In: Creutzfeldt W, Fölsch UR (eds) Delaving absorption as a therapeutic principle in metabolic disease. Thieme, Stuttgart New York, pp 70–78
Lee SM, Bustamante SA, Koldovsky O (1983) The effect of α-glucosidase inhibition on intestinal disacharidase activity in normal and diabetic mice. Metabolism 32:793–799
Keup U, Krause HP, Puls W, Thomas G (1982) Pharmacological studies on acarbose. I) Antihyperglycemic effects. In: Creutzfeldt W (ed) First International Symposium on Acarbose. Excerpta Medica, Amsterdam, pp 147–150
Willms B, Sachse G, Unger H (1980) Treatment of diabetes with a glycoside hydrolase inhibitor (Acarbose, Bay g 5421). Front Hormone Res 7:276–281
Reaven GM, Lardinois CM, Greenfield MS, Schwartz HC, Vreman HJ (1990) Effect of acarbose on carbohydrate and lipid metabolism in NIDDM patients poorly controlled by sulfonylureas. Diabetes Care 13:32–36
Gray SR, Olefsky JM (1982) Effect of a glucosidase inhibitor on the metabolic response of diabetic rats to a high carbohydrate diet, consisting of starch and sucrose, or glucose. Metabolism 31:88–92
Jeanrenaud B (1978) Hyperinsulinemia in obesity syndromes: its metabolic consequences and possible etiology. Metabolism 27:1881–1892
Coupé C, Perdereau D, Ferré P, Hitier Y, Narkewicz M, Girard J (1990) Lipogenic enzyme activities and mRNA in rat adipose tissue during weaning: role of the diet. Am J Physiol 258:E126-E133
Pond CM, Mattacks CA (1991) The effects of noradrenaline and insulin on lipolysis in adipocytes isolated from nine different adipose depots of guinea-pigs. Int J Obesity 15:609–618
Cantu RC, Goodman HM (1967) Effects of denervation and fasting on white adipose tissue. Am J Physiol 212:207–212
Issad T, Coupé C, Pastor-Anglada M, Ferré P, Girard J (1988) Development of insulin-sensitivity at weaning in the rat. Role of the nutritional transition. Biochem J 251:685–690
Demigné C, Yacoub C, Rémésy C (1986) Effects of absorption of large amounts of volatile fatty acids on rat liver metabolism. J Nutr 116:77–86
Ferré P, Pégorier JP, Marliss EB, Girard J (1978) Influence of exogenous fat and gluconeogenic substrates on glucose homeostasis in the newborn rat. Am J Physiol 234:E129-E136
Linn TC (1981) Purification and crystallization of rat liver fatty acid synthetase. Arch Biochem Biophys 209:613–619
Maeda H, Ikeda I, Sugano M (1975) Behavior of the liver key lipogenesis enzymes in rat fed with threonine imbalanced diet. Nutr Rep Int 12:61–66
Chang HC, Lane MD (1966) Purification and properties of liver mitochondrial phosphoenol pyruvate carboxykinase. J Biol Chem 241:2413–2420
Scherrer K, Darnell J (1962) Sedimentation characteristics of rapidly labelled RNA from HeLa cells. Biochem Biophys Res Commun 7:486–490
Leturque A, Postic C, Ferré P, Girard J (1991) Nutritional regulation of glucose transporter in muscle and adipose tissue of weaned rats. Am J Physiol 260:E588-E593
Foufelle F, Perdereau D, Gouhot B, Ferré P, Girard J (1992) Effect of diets rich in medium-chain and long-chain triglycerides on lipogenic-enzyme gene expression in liver and adipose tissue of the weaned rat. Eur J Biochem 208:381–387
Koevary SB (1990) Effects of acarbose on the development of diabetes in BB/Wor rats. Metabolism 39:865–870
Katovich MJ, Meldrum MJ, Vasselli JR (1991) Beneficial effects of dietary acarbose in the streptozotocin-induced diabetic rat. Metabolism 40:1275–1282
Vasselli JR, Haraczkiewicz E, Maggio CA, Greenwood MRC (1983) Effect of an alpha-glucosidase inhibitor (Acarbose BAY g 5421) on the development of obesity and food motivated behavior in Zucker (fa fa) rats. Pharmacol Biochem Behavior 19:85–89
Le Marchand-Brustel Y, Rochet N, Grémeaux T, Marot I, Van Obberghen E (1990) Effect of an α-glucosidase inhibitor on experimentally-induced obesity in mice. Diabetologia 33:24–30.
Radziuk J, Kemmer F, Morishima T, Berchtold P, Vranic M (1984) The effects of an alpha-glucoside hydrolase inhibitor on glycemia and the absorption of sucrose in man determined using a tracer method. Diabetes 33:207–213
Foufelle F, Gouhot B, Pégorier P et al. (1992) Glucose stimulation of lipogenic enzyme gene expression in cultured white adipose tissue. J Biol Chem 267:20543–20546
Pénicaud L, Ferré P, Terretaz J et al. (1987) Development of obesity in Zucker rats. Early insulin resistance in muscles but normal insulin sensitivity in white adipose tissue. Diabetes 36: 626–631
Krief S, Bazin R, Dupuy F, Lavau M (1988) Increased in vivo glucose utilization in 30-day-old obese Zucker rat: role of white adipose tissue. Am J Physiol 254:E342-E348
Pénicaud L, Ferré P, Assimacopoulos-Jeannet F et al. (1991) Increased gene expression of lipogenic enzymes and glucose transporter in white adipose tissue of suckling and weaned obese Zucker rats. Biochem J 279:303–308
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Maury, J., Issad, T., Perdereau, D. et al. Effect of acarbose on glucose homeostasis, lipogenesis and lipogenic enzyme gene expression in adipose tissue of weaned rats. Diabetologia 36, 503–509 (1993). https://doi.org/10.1007/BF02743265
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DOI: https://doi.org/10.1007/BF02743265