Influence of topiramate in the regulation of energy balance

Influence of topiramate in the regulation of energy balance Topiramate (TPM) is a novel neurotherapeutic agent currently indicated for the treatment of epilepsy and undergoing development for other central nervous system indications including neuropathic pain, bipolar disorder, and migraine prophylaxis. TPM is synthesized from d -fructose and contains a sulfamate moiety that is essential for its pharmacologic activity. TPM has been observed to significantly reduce body weight in patients treated for seizure, which has prompted the realization of preclinical studies to characterize the effects of TPM in the regulation of energy balance. Studies carried out in various strains of rats have provided good evidence for the ability of TPM to blunt energy deposition. Body composition analyses from rat trials have demonstrated that TPM inhibits fat deposition while reducing the activity of lipoprotein lipase (LPL) in various white adipose tissue depots. High doses of TPM (likely above the therapeutic dose range) have also been observed to reduce protein gain without catabolic effects. Although TPM cannot be described as a potent anorectic agent, it seems to have the ability to reduce food intake; significant reductions in food intake have been observed in female obese (fa/fa) Zucker rats and in female Wistar rats. TPM can also reduce energy deposition in the absence of alterations in food intake. This effect has been clearly emphasized in female lean (Fa/?) Zucker rats. In female Sprague–Dawley rats, TPM also increased energy expenditure and it has been observed to increase LPL activity in brown adipose tissue, which could indicate that TPM has the ability to enhance regulatory thermogenesis. In addition, TPM stimulates LPL activity in skeletal muscles, further emphasizing its potential to promote substrate oxidation. The mechanisms whereby TPM affects the regulation of energy balance have yet to be understood. TPM represents an antiepileptic drug (AED) with complex biochemical/pharmacologic actions. Its negative effects on energy deposition cannot be readily predicted from these actions, as AEDs are generally expected to stimulate body weight gain. Recent data, obtained from investigations aimed at assessing the effects of TPM on neuropeptidergic systems involved in the regulation of energy balance, have failed to demonstrate any significant effects of TPM on the neuropeptide Y and proopiomelanocortin systems. In conclusion, it is clear that TPM can reduce fat deposition by either reducing food intake or stimulating energy expenditure. The mechanisms whereby an AED such as TPM controls food intake and energy expenditure remains to be delineated.©1999 ASCRS and ESCRS http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nutrition Elsevier

Influence of topiramate in the regulation of energy balance

Loading next page...
 
/lp/elsevier/influence-of-topiramate-in-the-regulation-of-energy-balance-1I1hlDDVht
Publisher
Elsevier
Copyright
Copyright © 2000 Elsevier Science Inc.
ISSN
0899-9007
DOI
10.1016/S0899-9007(00)00452-4
Publisher site
See Article on Publisher Site

Abstract

Topiramate (TPM) is a novel neurotherapeutic agent currently indicated for the treatment of epilepsy and undergoing development for other central nervous system indications including neuropathic pain, bipolar disorder, and migraine prophylaxis. TPM is synthesized from d -fructose and contains a sulfamate moiety that is essential for its pharmacologic activity. TPM has been observed to significantly reduce body weight in patients treated for seizure, which has prompted the realization of preclinical studies to characterize the effects of TPM in the regulation of energy balance. Studies carried out in various strains of rats have provided good evidence for the ability of TPM to blunt energy deposition. Body composition analyses from rat trials have demonstrated that TPM inhibits fat deposition while reducing the activity of lipoprotein lipase (LPL) in various white adipose tissue depots. High doses of TPM (likely above the therapeutic dose range) have also been observed to reduce protein gain without catabolic effects. Although TPM cannot be described as a potent anorectic agent, it seems to have the ability to reduce food intake; significant reductions in food intake have been observed in female obese (fa/fa) Zucker rats and in female Wistar rats. TPM can also reduce energy deposition in the absence of alterations in food intake. This effect has been clearly emphasized in female lean (Fa/?) Zucker rats. In female Sprague–Dawley rats, TPM also increased energy expenditure and it has been observed to increase LPL activity in brown adipose tissue, which could indicate that TPM has the ability to enhance regulatory thermogenesis. In addition, TPM stimulates LPL activity in skeletal muscles, further emphasizing its potential to promote substrate oxidation. The mechanisms whereby TPM affects the regulation of energy balance have yet to be understood. TPM represents an antiepileptic drug (AED) with complex biochemical/pharmacologic actions. Its negative effects on energy deposition cannot be readily predicted from these actions, as AEDs are generally expected to stimulate body weight gain. Recent data, obtained from investigations aimed at assessing the effects of TPM on neuropeptidergic systems involved in the regulation of energy balance, have failed to demonstrate any significant effects of TPM on the neuropeptide Y and proopiomelanocortin systems. In conclusion, it is clear that TPM can reduce fat deposition by either reducing food intake or stimulating energy expenditure. The mechanisms whereby an AED such as TPM controls food intake and energy expenditure remains to be delineated.©1999 ASCRS and ESCRS

Journal

NutritionElsevier

Published: Oct 1, 2000

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off