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Science 2 August 2002:
Vol. 297. no. 5582, pp. 843 - 845
DOI: 10.1126/science.1073160
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Reports

beta AR Signaling Required for Diet-Induced Thermogenesis and Obesity Resistance

Eric S. Bachman, Harveen Dhillon, Chen-Yu Zhang, Saverio Cinti, Antonio C. Bianco, Brian K. Kobilka, Bradford B. Lowell

Excessive caloric intake is thought to be sensed by the brain, which then activates thermogenesis as a means of preventing obesity. The sympathetic nervous system, through beta -adrenergic receptor (beta AR) action on target tissues, is likely the efferent arm of this homeostatic mechanism. To test this hypothesis, we created mice that lack the three known beta ARs (beta -less mice). beta -less mice on a Chow diet had a reduced metabolic rate and were slightly obese. On a high-fat diet, beta -less mice, in contrast to wild-type mice, developed massive obesity that was due entirely to a failure of diet-induced thermogenesis. These findings establish that beta ARs are necessary for diet-induced thermogenesis and that this efferent pathway plays a critical role in the body's defense against diet-induced obesity.

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