betaAR signaling required for diet-induced thermogenesis and obesity resistance

Science. 2002 Aug 2;297(5582):843-5. doi: 10.1126/science.1073160.

Abstract

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 (betaAR) 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 betaARs (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 betaARs are necessary for diet-induced thermogenesis and that this efferent pathway plays a critical role in the body's defense against diet-induced obesity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism
  • Animals
  • Basal Metabolism / drug effects
  • Body Temperature / drug effects
  • Body Weight / drug effects
  • Body Weight / genetics
  • Diet*
  • Dietary Fats / administration & dosage
  • Dietary Fats / pharmacology
  • Energy Intake
  • Female
  • Homeostasis / drug effects
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Knockout
  • Obesity / blood
  • Obesity / genetics
  • Obesity / metabolism*
  • Obesity / prevention & control
  • Oxygen Consumption / drug effects
  • Phenotype
  • Receptors, Adrenergic, beta / genetics
  • Receptors, Adrenergic, beta / metabolism*
  • Signal Transduction* / drug effects
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / physiology
  • Thermogenesis / genetics
  • Thermogenesis / physiology*

Substances

  • Dietary Fats
  • Receptors, Adrenergic, beta