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

Nature volume 366, pages 740–742 (1993)Cite this article

Abstract

BROWN adipose tissue, because of its capacity for uncoupled mitochondria! respiration1,2, has been implicated as an important site of facultative energy expenditure3–5. This has led to speculation that this tissue normally functions to prevent obesity3–5. 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 hypertrophy6. Here we have used a transgenic toxigene approach7,8 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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Author notes

  1. Bert B. Boyer

    Present address: Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, Alaska, 99775, USA

Authors and Affiliations

  1. Charles A. Dana Research Institute and Harvard-Thorndike Laboratory of Beth Israel Hospital, Department of Medicine,

    Bradford B. Lowell, Vedrana S-Susulic, Andreas Hamann & Jeffrey S. Flier

  2. Department of Pathology, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts, 02215, USA

    Joel A. Lawitts

  3. Department of Biochemistry, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, K1H 8M5, Canada

    Jean Himms-Hagen

  4. Jackson Laboratory, 600 Main Street, Bar Harbor, Maine, 04609, USA

    Bert B. Boyer & Leslie P. Kozak

Authors
  1. Bradford B. Lowell
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Lowell, B., S-Susulic, V., Hamann, A. et al. Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature 366, 740–742 (1993). https://doi.org/10.1038/366740a0

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