Cited by 250Adipose Tissue and MetabolismMitochondrial Function and PathologyPharmacology and Obesity Treatment

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Mitochondrial uncoupling as a target for drug development for the treatment of obesity.

Harper, J. A., Dickinson, K., Brand, M. D.·2001·Obesity Reviews

DOI 10.1046/j.1467-789x.2001.00043.x

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Abstract

Mitochondrial proton cycling is responsible for a significant proportion of basal or standard metabolic rate, so further uncoupling of mitochondria may be a good way to increase energy expenditure and represents a good pharmacological target for the treatment of obesity. Uncoupling by 2,4-dinitrophenol has been used in this way in the past with notable success, and some of the effects of thyroid hormone treatment to induce weight loss may also be due to uncoupling. Diet can alter the pattern of phospholipid fatty acyl groups in the mitochondrial membrane, and this may be a route to uncoupling in vivo. Energy expenditure can be increased by stimulating the activity of uncoupling protein 1 (UCP1) in brown adipocytes either directly or through beta 3-adrenoceptor agonists. UCP2 in a number of tissues, UCP3 in skeletal muscle and the adenine nucleotide translocase have also been proposed as possible drug targets. Specific uncoupling of muscle or brown adipocyte mitochondria remains an attractive target for the development of antiobesity drugs.

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Authors: Harper, J. A., Dickinson, K., & Brand, M. D.
Affiliations: University of Cambridge (GB)
MRC Mitochondrial Biology Unit (GB)
Corresponding author: Brand, M. D.
ORCID: Brand, M. D.
Venue: Obesity Reviews
Publisher: Wiley
Published: 2001-11
Volume: 2
Issue: 4
Pages: 255-265
ISSN: 1467-7881 (ISSN-L)
1467-789X
DOI: 10.1046/j.1467-789x.2001.00043.x
OpenAlex: W1979144331
Cited by: 250
References: 119
Citations by year: 2026: 2 · 2025: 1 · 2024: 6 · 2023: 9 · 2022: 7 · 2021: 6 · 2020: 19 · 2019: 9 · 2018: 12 · 2017: 9 · 2016: 11 · 2015: 19 · 2014: 25 · 2013: 12 · 2012: 15
FWCI: 0.53
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 2440 d)
Locations: Obesity Reviews (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Health Sciences › Medicine › Pharmacology (medical) › Pharmacology and Obesity Treatment
Keywords: mitochondrial uncoupling, obesity treatment, energy expenditure, UCP1, brown adipocytes, beta3-adrenergic agonists, UCP2, UCP3, adenine nucleotide translocase, 2,4-dinitrophenol, thyroid hormones, mitochondrial membrane phospholipids, anti-obesity drugs
MeSH terms: Uncoupling Protein 1, Basal Metabolism, Carrier Proteins, Energy Metabolism, Humans, Ion Channels, Membrane Proteins, Mitochondria, Obesity, Weight Loss, Anti-Obesity Agents, Mitochondrial Proteins

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Mitochondrial uncoupling as a target for drug development for the treatment of obesity.

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