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

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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