Decreased incorporation of glucose into lipids and increased lactate production by adipose tissue after long-term treatment of rats with D-fenfluramine.
Male rats were treated with ten daily doses of 10 mg of D-fenfluramine/kg. Body weight decreased after days 1 and 2, but thereafter the weight gain paralleled that of the control rats. After the tenth injection there were decreases in the weights of the epididymal fat pads, their fat content, and the average size of the adipocytes after collaginase digestion. The rate of glucose uptake by incubated pieces of adipose tissue was maintained after D-fenfluramine treatment, and the production of lactate increased. The incorporation of glucose into fatty acids by adipose tissue pieces decreased by 65-74% after treatment with D-fenfluramine. This effect was not reversed by adding insulin or phenylisopropyladenosine to the incubations. D-Fenfluramine also decreased the incorporation of glucose into glyceride-glycerol, but this effect was less pronounced than that for fatty acid synthesis. Direct addition of D-fenfluramine to the incubation inhibited lipid synthesis from [14C]glucose but only at drug concentrations above 1 mM. It is concluded that the treatment of rats with D-fenfluramine modifies the metabolic balance of adipose tissue so as to direct glucose metabolism away from lipid synthesis and towards lactate production. This could be a significant mechanism in the overall loss of adipose tissue mass caused by the administration of D-fenfluramine.
al-Sieni
A I
AI
Department of Biochemistry, Faculty of Medicine, University of Alberta, Edmonton, Canada.
Plested
C P
CP
Rolland
Y
Y
Brindley
D N
DN
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000096:biosynthesis; D005277:Fenfluramine / Q000008:administration & dosage* / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006868:Hydrolysis; D007773:Lactates / Q000378:metabolism*; D008055:Lipids / Q000096:biosynthesis*; D008297:Male; D003012:Microbial Collagenase; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000096:biosynthesis
D005227:Fatty Acids; D007773:Lactates; D008055:Lipids; D014280:Triglycerides; D002245:Carbon Dioxide; D005277:Fenfluramine; D003012:Microbial Collagenase; D005947:Glucose