Human Uncoupling Protein‐3 and Obesity: An Update

Hesselink, Matthijs K.C.; Mensink, Marco; Schrauwen, Patrick

doi:10.1038/oby.2003.192

Cited by 85Adipose Tissue and MetabolismMitochondrial Function and PathologyMetabolism, Diabetes, and Cancer

Human Uncoupling Protein‐3 and Obesity: An Update

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Hesselink, Matthijs K.C., Mensink, Marco, Schrauwen, Patrick·2003·Obesity Research

DOI 10.1038/oby.2003.192

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Abstract

The cloning of the uncoupling protein (UCP)1 homologs UCP2 and UCP3 has raised considerable interest in the mechanism. The expression of UCP3 mainly in skeletal muscle mitochondria and the potency of the skeletal muscle as a thermogenic organ made UCP3 an attractive target for studies toward manipulation of energy expenditure to fight disorders such as obesity and type 2 diabetes. Overexpressing UCP3 in mice resulted in lean, hyperphagic mice. However, the lack of an apparent phenotype in mice lacking UCP3 triggered the search for alternative functions of UCP3. The observation that fatty acid levels significantly affect UCP3 expression has given UCP3 a position in fatty acid handling and/or oxidation. Emerging data indicate that the primary physiological role of UCP3 may be the mitochondrial handling of fatty acids rather than the regulation of energy expenditure through thermogenesis. It has been proposed that UCP3 functions to export fatty acid anions away from the mitochondrial matrix. In doing so, fatty acids are exchanged with protons, explaining the uncoupling activity of UCP3. The exported fatty acid anions may originate from hydrolysis of fatty acid esters by a mitochondrial thioesterase, or they may have entered the mitochondria as nonesterified fatty acids by incorporating into and flip‐flopping across the mitochondrial inner membrane. Regardless of the origin of the fatty acid anions, this putative function of UCP3 might be of great importance in protecting mitochondria against fatty acid accumulation and may help to maintain muscular fat oxidative capacity.

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An important role for UCP3 may be to export fatty acids.
“In addition, evidence indicates that an important role for UCP3 may be to export fatty acids (136, 289).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [136]

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Research works printed but not linked: 3

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Authors: Hesselink, M. K. C., Mensink, M., & Schrauwen, P.
Affiliations: Maastricht University (NL)
Corresponding author: Hesselink, Matthijs K.C.
ORCID: Hesselink, Matthijs K.C.
Mensink, Marco
Schrauwen, Patrick
Venue: Obesity Research
Publisher: Wiley
Published: 2003-12
Volume: 11
Issue: 12
Pages: 1429-1443
ISSN: 1071-7323 (ISSN-L)
1550-8528
DOI: 10.1038/oby.2003.192
OpenAlex: W2023262549
Cited by: 85
References: 98
Citations by year: 2026: 1 · 2025: 2 · 2024: 5 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 3 · 2017: 4 · 2016: 2 · 2014: 4 · 2013: 5 · 2012: 6
FWCI: 0.98
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 3202 d)
Locations: Obesity Research (publishedVersion)
PubMed (publishedVersion)
Research Publications (Maastricht University) (publishedVersion, other-oa)
Socio-Environmental Systems Modeling (acceptedVersion)
Research Publications (Maastricht University) (submittedVersion, other-oa)
Data Archiving and Networked Services (DANS) (submittedVersion)
Funders: Koninklijke Nederlandse Akademie van Wetenschappen
Topics: Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: UCP3, obesity, skeletal muscle mitochondria, fatty acid oxidation, thermogenesis, energy expenditure, type 2 diabetes
MeSH terms: Uncoupling Protein 3, Animals, Carrier Proteins, Energy Metabolism, Fatty Acids, Humans, Ion Channels, Mitochondria, Muscle, Obesity, Oxidative Phosphorylation, Mitochondrial Proteins, Mice

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Human Uncoupling Protein‐3 and Obesity: An Update

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