Decreased serum lipids, serum insulin and triacylglycerol synthesis in adipose tissue of JCR:LA-corpulent rats treated with benfluorex.
Rats of the JCR:LA-corpulent strain were treated with benfluorex daily at a dose of 25 mg/kg body weight. This strain of rat, if homozygous for the cp gene (cp/cp), is hyperphagous, obese, hypertriglyceridemic, insulin resistant and in the case of male rats, atherosclerosis prone. The benfluorex treatment produced a sharp reduction in food intake which remained suppressed despite recovery toward normal after 2 weeks of treatment. This was accompanied by sustained decreases in body weight and adipose tissue mass. The ability of adipose tissue from female rats to take up glucose and convert it to lactate, glyceride-glycerol and fatty acids was decreased. This decrease was largely due to decreased adipose tissue mass. The serum concentrations of glucose, lactate, triacylglycerol, cholesterol, phospholipids and insulin were decreased in both sexes. The treatment also improved glucose tolerance and decreased corticosterone concentrations in male rats only. While reduction of food consumption contributes to the effects seen, benfluorex clearly had significant direct metabolic effects. The effects are consistent with an improved insulin sensitivity leading to a decrease in circulating triacylglycerol. The changes produced by benfluorex are all in directions that should inhibit atherogenesis in this animal model for the human obesity/hypertriglyceridemia/insulin resistant syndrome.
Brindley
D N
DN
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Hales
P
P
al-Sieni
A I
AI
Russell
J C
JC
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D005247:Feeding Behavior; D005260:Female; D005277:Fenfluramine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006728:Hormones / Q000097:blood; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood*; D008055:Lipids / Q000097:blood*; D008297:Male; D009765:Obesity / Q000235:genetics; D051381:Rats; D014280:Triglycerides / Q000096:biosynthesis*
D006728:Hormones; D000960:Hypolipidemic Agents; D007328:Insulin; D008055:Lipids; D014280:Triglycerides; D005277:Fenfluramine; C001584:benfluorex; D005947:Glucose