Abstract
OBJECTIVE: The effects of topiramate (TPM) on components of energy balance were tested in male and female rats that were (i) left intact, (ii) castrated or (iii) castrated with replacement therapies consisting of testosterone administration in orchidectomized (OCX) rats and of estradiol or progesterone treatments in ovariectomized (OVX) rats.
METHODS: TPM was mixed into the diet and administered at a dose of 60 mg per kg of body weight. Male and female rats were treated for 28 and 35 days, respectively. At the end of the treatment period, variables of energy balance and determinants of lipid and glucose metabolism were assessed.
RESULTS: TPM reduced energy and fat gains in both male and female rats either in the absence or in the presence of hormone replacement therapies. In male rats, it also decreased food intake, protein gain and energetic efficiency. In female animals, TPM reduced energetic efficiency while it stimulated lipoprotein lipase activity in brown adipose tissue. TPM also reduced plasma glucose and plasma leptin levels in female rats as well as plasma insulin and liver triglycerides in male animals. As expected, castration and sex hormones also strongly influenced energy balance. In male rats, OCX led to a decrease in energy and protein gains that was blocked by treatment with testosterone. In female rats, OVX caused increases in energy, fat and protein gains that were prevented by treatment with estradiol.
CONCLUSION: In female rats, the effects of TPM on fat and energy gains were clearly not influenced by the sex hormone status of the rats. In male animals, there was also no interaction of TPM and the status of sex hormones on energy balance, suggesting that OCX and testosterone minimally interfere with the action of TPM on energy balance. The effects of TPM on energy balance were accounted for by a decrease in energetic efficiency, resulting from an effect exerted by the drug on both energy intake and thermogenesis. The present results also suggest that TPM can enhance insulin sensitivity.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Shank RJ, Gardocki JF, Streeter AJ, Maryanoff BE . An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics and mechanism of action Epilepsia 2000 41: S3–S9.
White HS, Brown SD, Woodhead JH, Skeen GA, Wolf HH . Topiramate enhances GABA-mediated chloride flux and GABA-evoked currents in mouse brain neurons and increases seizure threshold Epilepsy Res 1997 28: 167–179.
White HS, Skeen GA, Woodhead J, Wolf HH . Topiramate modulates GABA-evoked currents in murine cortical neurons by non-benzodiazepine mechanism Epilepsia 2000 41: S17–S20.
Gibbs JW, Sombati S, DeLorenzo RJ, Coulter DA . Cellular actions of topiramate: blockade of kainate-evoked inward currents in cultured hippocampal neurons Epilepsia 2000 41: S10–S16.
Skradski S, White HS . The novel antiepileptic drug topiramate blocks kainate-evoked cobalt influx into cultured neurons Epilepsia 2000 41: S45–S47.
Taverna S, Sancini G, Mantegazza M, Franceschetti S, Avanzini G . Inhibition of transient and persistent Na+ current fractions by the new anticonvulsant topiramate J Pharm Exp Ther 2000 288: 960–968.
Zona C, Ciotti NIT, Avoli M . Topiramate attenuates voltage-gated sodium currents in rat cerebellar granule cells in culture Neurosci Lett 1997 231: 123–126.
DeLorenzo RJ, Sombati S, Coulter DA . Effects of topiramate on sustained repetitive firing and spontaneous recurrent seizure discharges in cultured hippocampal neurons Epilepsia 2000 41: S40–S44.
Wu SP, Tsai JJ, Gean PW . Frequency-dependent inhibition of neuronal firing by topiramate in hippocampal slices Br J Pharmac 1999 125: 826–832.
McLean MJ, Bukhari AA, Wamil AW . Effects of topiramate on sodium-dependent action potential firing by mouse spinal cord neurons in cell culture Epilepsia 2000 41: S21–S24.
Zhang XL, Velumian A, Jones OT, Carlen PL . Modulation of high voltage-activated calcium channels in dentate granule cells by topiramate Epilepsia 2000 41: S52–S60.
Dodgson SJ, Shank RP, Maryanoff BE . Topiramate as an inhibitor of carbonic anhydrase isozymes Epilepsia 2000 41: S35–S39.
Gordon A, Price LH . Mood stabilization and weight loss with topiramate. [Letter.] Am J Psychiat 1999 156: 968–969.
Ketter TA, Post RM, Theodore WH . Positive and negative psychiatric effects of antiepileptic drugs in patients with seizure disorders. [In Process Citation.] Neurology 1999 53: S53–S67.
Baulac M, Arzimanoglou A, Semah F, Cavalcanti D . [Therapeutic options provided by new antiepileptic drugs.] Rev Neurol (Paris) 1997 155: 21–33.
York DA, Singer L, Thomas S, Bray GA . 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 Nutrition 2000 16: 967–975.
Biton V, Montouris GD, Ritter F, Riviello JJ, Reife R, Lim P, Pledger G . A randomized, placebo-controlled study of topiramate in primary generalized tonic-clonic seizures. Topiramate YTC Study Group Neurology 1999 52: 1330–1337.
Picard F, Deshaies Y, Lalonde J, Samson P, Richard D . Topiramate reduces energy and fat gains in lean (Fa/?) and obese (fa/fa) Zucker rats Obes Res 2000 8: 656–663.
Richard D, Ferland J, Lalonde J, Samson P, Deshaies Y . Influence of topiramate in the regulation of energy balance Nutrition 2000 16: 961–966.
Smith U, Axelsen M, Hellebo-Johanson E, Lundgren B, Ben-Menachen E . Topiramate, a novel antiepileptic drug, reduces body weight and food intake in obesity Obes Res 2000 8: 10S.
Wade GN, Gray JM, Bartness TJ . Gonadal influences on adiposity Int J Obes 1985 9: 83–92.
Rivest S, Landry J, Richard D . Effect of exercise training on energy balance of orchidectomized rats Am J Physiol 1989 257: R550–R555.
Richard D . Effects of ovarian hormones on energy balance and brown adipose tissue thermogenesis Am J Physiol 1986 250: R245–R249.
Waynforth HB . Experimental and surgical technique in the rat Academic Press: London 1980.
Labrie C, Simard J, Zhao HF, Belanger A, Pelletier G, Labrie F . Stimulation of androgen-dependent gene expression by the adrenal precursors dehydroepiandrosterone and androstenedione in the rat ventral prostate Endocrinology 1989 124: 2745–2754.
Picard F, Deshaies Y, Lalonde J, Samson P, Labrie C, Belanger A, Labrie F, Richard D . Effects of the estrogen antagonist EM-652.HCl on energy balance and lipid metabolism in ovariectomized rats. [In Process Citation.] Int J Obes Relat Metab Disord 2000 24: 830–840.
Deshaies Y, Dagnault A, Lalonde J, Richard D . Interaction of corticosterone and gonadal steroids on lipid deposition in the female rat Am J Physiol Endocrinol Met 1997 36: E355–E362.
Dagnault A, Deshaies Y, Richard D . Effects of the 5-hydroxytryptamine agonist Dl-fenfluramine on energy balance in rats: influence of gender Int J Obes Relat Metab Disord 1993 17: 367–373.
Lofti M, MacDonald IA, Stock MJ . Energy losses associated with oven-drying and the preparation of rat carcasses for analysis Br J Nutr 1976 36: 305–309.
Webster AJF . Energetics of maintenance and growth. In: Girardier L, Stock M (eds). Mammalian thermogenesis Chapman and Hall: London 1983 178–207.
Barr HG, Mckracken KJ . High efficiency of energy utilization in ‘cafeteria’-and force-fed rats kept at 29° Br J Nutr 1984 51: 379–387.
Folch J, Lees M, Sloane Stanley GH . A simple method for the isolation and purification of total lipids from animal tissues J Biol Chem 1957 226: 497–509.
Deshaies Y, Geloen A, Paulin A, Bukowiecki LJ . Restoration of lipoprotein lipase activity in insulin-deficient rats by insulin infusion is tissue-specific Can J Physiol Pharmac 1991 69: 746–751.
Belfrage P, Vaughan M . Simple liquid–liquid partition system for isolation of labeled oleic acid from mixtures with glycerides J Lipid Res 1969 10: 341–344.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ . Protein measurement with the folin phenol reagent J Biol Chem 1951 193: 265–275.
Richard D, Arnold J, LeBlanc J . Energy balance in exercise-trained rats acclimated at two environmental temperatures J Appl Physiol 1986 60: 1054–1059.
Carneheim C, Nedergaard J, Cannon B . Cold-induced b-adrenergic recruitment of lipoprotein lipase in brown fat is due to increased transcription Am J Physiol 1988 254: E155–E161.
Trayhurn P, Richard D . Brown adipose tissue thermogenesis and the energetics of pregnancy and lactation in rodents Biochem Soc Trans 1985 13: 826–827.
Trayhurn P . Brown adipose tissue—from thermal physiology to bioenergetics J Biosci 1993 18: 161–173.
Acknowledgements
This study was supported by funding from The RW Johnson Pharmaceutical Research Institute (Raritan, NJ, USA).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Richard, D., Picard, F., Lemieux, C. et al. The effects of topiramate and sex hormones on energy balance of male and female rats. Int J Obes 26, 344–353 (2002). https://doi.org/10.1038/sj.ijo.0801873
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ijo.0801873
Keywords
This article is cited by
-
Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand?
Current Obesity Reports (2021)
-
Synchronous neuronal interactions in rat hypothalamic culture: a novel model for the study of network dynamics in metabolic disorders
Experimental Brain Research (2021)
-
Centrally Acting Agents for Obesity: Past, Present, and Future
Drugs (2018)
-
Treating Epilepsy in the Setting of Medical Comorbidities
Current Treatment Options in Neurology (2014)
-
Antiobesity Pharmacotherapy: New Drugs and Emerging Targets
Clinical Pharmacology & Therapeutics (2013)