Development of obesity in transgenic mice after genetic ablation of brown adipose tissue
Abstract
Brown adipose tissue, because of its capacity for uncoupled mitochondrial respiration, has been implicated as an important site of facultative energy expenditure. This has led to speculation that this tissue normally functions to prevent obesity. Attempts to ablate or denervate brown adipose tissue surgically have been uninformative because it exists in diffuse depots and has substantial capacity for regeneration and hypertrophy. Here we have used a transgenic toxigene approach to create two lines of transgenic mice with primary deficiency of brown adipose tissue. At 16 days, both lines have decreased brown fat and obesity. In one line, brown fat subsequently regenerates and obesity resolves. In the other line, the deficiency persists and obesity, with its morbid complications, advances. Obesity develops in the absence of hyperphagia, indicating that brown fat deficient mice have increased metabolic efficiency. As obesity progresses, transgenic animals develop hyperphagia. This study supports a critical role for brown adipose tissue in the nutritional homeostasis of mice.
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Ablation of BAT leads to reduced energy expenditure and increased obesity on high fat diet.
“Conversely, ablation of BAT leads to reduced energy expenditure and increased obesity on high fat diet 75.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [75]
The UCP-DTA mouse develops a mild degree of obesity and insulin resistance that is less severe than that observed in mice with mutations in leptin or its receptor.
“The UCP-DTA mouse in which a diphtheria-toxin transgene is expressed in brown adipose tissue (BAT) resulting in BAT ablation develop a mild degree of obesity and insulin resistance that is less severe than that observed in mice with mutations in leptin or its receptor (215).”
From Cardiac remodeling in obesity (2008) · cites this paper as [215]
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- Authors
- Lowell, B. B., S-Susulic, V., Hamann, A., Lawitts, J. A., Himms-Hagen, J., Boyer, B. B., Kozak, L. P., & Flier, J. S.
- Affiliations
- Harvard University (US)
- University of Alaska Fairbanks (US)
- Jackson Laboratory (US)
- Venue
- Nature
- Published
- 1993-12
- Volume
- 366
- Issue
- 6457
- Pages
- 740-742
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2021760176
- Cited by
- 1,075
- References
- 26
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 20 · 2023: 25 · 2022: 29 · 2021: 36 · 2020: 53 · 2019: 38 · 2018: 54 · 2017: 41 · 2016: 53 · 2015: 52 · 2014: 50 · 2013: 54 · 2012: 39
- FWCI
- 11.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- brown adipose tissue, obesity, transgenic mice, hyperphagia, energy expenditure, nutritional homeostasis, obesity complications
- MeSH terms
- Uncoupling Protein 1, Animals, Body Weight, Adipose Tissue, Brown, Carrier Proteins, Diphtheria Toxin, Eating, Female, Homeostasis, Ion Channels, Male, Membrane Proteins, Mice, Transgenic, Obesity, Mitochondrial Proteins, Mice
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