Expression of the mitochondrial uncoupling protein gene from the aP2 gene promoter prevents genetic obesity.
Open accessAbstract
The brown fat-specific mitochondrial uncoupling protein (UCP) provides a mechanism for generating heat by uncoupling respiration and oxidative phosphorylation. It has been suggested that this system of thermogenesis can provide a defense against obesity. To test this idea, we created a transgenic mouse in which the fat-specific aP2 gene promoter directed Ucp expression in white fat and provided for the constitutive expression of Ucp in brown fat. Transgenic mice showed both Ucp mRNA and immunoreactive UCP in white fat at 2-10% the level normally measured in brown fat. A reduction in subcutaneous fat of aP2-Ucp C57BL/6J mice was observed at 3 mo of age. When the transgene was expressed in Avy genetically obese mice reductions in total body weight and subcutaneous fat stores were observed. Female transgenic Avy mice at 13 mo of age weighed 35 grams, a weight indistinguishable from nontransgenic C57BL/6J mice. Gonadal fat showed an increase in a novel adipocyte derivative that did not accumulate lipids and that constituted approximately 80% of the mass of the tissue in Avy transgenic. A major effect of aP2-Ucp in brown fat was to reduce endogenous gene expression by as much as 95%. The results suggest that UCP synthesized from the aP2 gene promoter is thermogenically active and capable of reducing fat stores.
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Transgenic mice with UCP1 expression in white fat display a lean phenotype.
“Conversely, transgenic mice with UCP1 expression in white fat display lean phenotype 34,35.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [34]
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- Authors
- Kopecky, J., Clarke, G., Enerbäck, S., Spiegelman, B., & Kozak, L. P.
- Affiliations
- Harvard University (US)
- Czech Academy of Sciences (CZ)
- Venue
- Journal of Clinical Investigation
- Published
- 1995-12-01
- Volume
- 96
- Issue
- 6
- Pages
- 2914-2923
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC186003
- OpenAlex
- W1974418613
- Cited by
- 553
- References
- 31
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 10 · 2023: 11 · 2022: 9 · 2021: 14 · 2020: 23 · 2019: 27 · 2018: 22 · 2017: 28 · 2016: 29 · 2015: 32 · 2014: 34 · 2013: 30 · 2012: 18
- FWCI
- 5.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- Pfizer
- Grantová Agentura České Republiky
- National Institutes of Health (1r01hd029149-01a1)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-31405)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-29149)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- mitochondrial uncoupling proteins, UCP, brown adipose tissue, white adipose tissue, thermogenesis, genetic obesity, transgenic mice, subcutaneous adipose tissue, gonadal fat, adipocytes, fat mass reduction
- MeSH terms
- Uncoupling Protein 1, Fatty Acid-Binding Protein 7, Adipose Tissue, Animals, Base Sequence, Body Temperature Regulation, Body Weight, Adipose Tissue, Brown, Carrier Proteins, Exons, Female, Ion Channels, Male, Membrane Proteins, Mice, Inbred C57BL, Mice, Obese, Mice, Transgenic, Mitochondria, Molecular Sequence Data, Neoplasm Proteins, Nerve Tissue Proteins, Obesity, Organ Specificity, Organ Size, Promoter Regions, Genetic, Regulatory Sequences, Nucleic Acid, Sex Characteristics, Genetic Variation, Restriction Mapping, Polymerase Chain Reaction, DNA Primers, Myelin P2 Protein, Mitochondrial Proteins, Fatty Acid-Binding Proteins, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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