Development of obesity in transgenic mice after genetic ablation of brown adipose tissue.
Adipose Tissue, Brown, Animals, Body Weight, Carrier Proteins, Diphtheria Toxin, Eating, Female, Homeostasis, Ion Channels, Male, Membrane Proteins, Mice, Mice, Transgenic, Mitochondrial Proteins, Obesity
Nature Publishing Group
Nature 1993; 366(6457):740-2.
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.
Lowell, B B; S-Susulic, V; Hamann, A; Lawitts, J A; Himms-Hagen, J; Boyer, B B; Kozak, L P; and Flier, J S, "Development of obesity in transgenic mice after genetic ablation of brown adipose tissue." (1993). Faculty Research 1990 - 1999. 477.