Cited by 1,075Adipose Tissue and MetabolismRegulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic Diseases

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Development of obesity in transgenic mice after genetic ablation of brown adipose tissue

Lowell, Bradford B., S-Susulic, Vedrana, Hamann, Andreas, Lawitts, Joel A., Himms-Hagen, Jean, Boyer, Bert B., Kozak, Leslie P., Flier, Jeffrey S.·1993·Nature

DOI 10.1038/366740a0

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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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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)
ORCID: Lowell, Bradford B.
Boyer, Bert B.
Kozak, Leslie P.
Flier, Jeffrey S.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1993-12
Volume: 366
Issue: 6457
Pages: 740-742
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/366740a0
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 (medical) › Adipose Tissue and Metabolism
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › 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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Development of obesity in transgenic mice after genetic ablation of brown adipose tissue

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