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.