Effect of acarbose on glucose homeostasis, lipogenesis and lipogenic enzyme gene expression in adipose tissue of weaned rats.
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.
Maury
J
J
Centre de Recherche sur l'Endocrinologie Moléculaire, et le Développement CNRS, Meudon, France.
Issad
T
T
Perdereau
D
D
Gouhot
B
B
Ferré
P
P
Girard
J
J
D020909:Acarbose; D000103:Acetyl-CoA Carboxylase / Q000096:biosynthesis / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000096:biosynthesis / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000378:metabolism; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D014312:Trisaccharides / Q000494:pharmacology*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D007773:Lactates; D008055:Lipids; D012333:RNA, Messenger; D014312:Trisaccharides; D064429:Fatty Acid Synthases; D000103:Acetyl-CoA Carboxylase; D005947:Glucose; D020909:Acarbose