Effect of topiramate on body weight and body composition of osborne-mendel rats fed a high-fat diet: alterations in hormones, neuropeptide, and uncoupling-protein mRNAs.
The effects of topiramate on food intake and body composition were investigated in rats fed a high-fat diet and compared with rats that were pair fed or treated with D-fenfluramine. Topiramate (40 mg. kg. d for 80 d) reduced body-weight gain in a manner similar to that of pair-fed rats and D-fenfluramine-treated rats. The reduction in body fat accounted for all the weight reduction after topiramate treatment but not after pair feeding or D-fenfluramine treatment. Topiramate reduced food intake acutely and increased metabolic rate. There were also significant reductions in leptin, insulin, and corticosterone. In the hypothalamus, topiramate increased mRNA for neuropeptide Y, reduced mRNA for neuropeptide-Y Y1 and Y5 receptors, corticotropin-releasing hormone (CRH), and type II glucocorticoid receptors but had no effect on mRNA levels for the short or long form of the leptin receptor. In peripheral tissues, topiramate reduced leptin mRNA in adipose tissue, had no effect on uncoupling protein 1 mRNA in brown adipose tissue but had tissue-selective effects on uncoupling proteins 2 and 3 mRNA levels in white and brown adipose tissues and muscle. In conclusion, topiramate is an effective inhibitor of weight gain in rats on a high-fat diet, but the mechanism through which the change in energy balance is achieved is unclear.
York
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Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA. yorkda@pbrc.edu
Singer
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L
Thomas
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Bray
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GA
D000818:Animals; D001823:Body Composition / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects*; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage; D004435:Eating / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects*; D005632:Fructose / Q000031:analogs & derivatives / Q000494:pharmacology*; D006728:Hormones / Q000235:genetics; D007473:Ion Channels; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D023421:Models, Animal; D009479:Neuropeptides / Q000187:drug effects / Q000235:genetics; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011506:Proteins / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D051381:Rats; D013997:Time Factors; D000077236:Topiramate; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D004041:Dietary Fats; D006728:Hormones; D007473:Ion Channels; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D009479:Neuropeptides; D018696:Neuroprotective Agents; D011506:Proteins; D012333:RNA, Messenger; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D000077236:Topiramate; D005632:Fructose