βAR Signaling Required for Diet-Induced Thermogenesis and Obesity Resistance

TLDR

Excessive caloric intake is sensed by the brain, which activates thermogenesis to prevent obesity, likely via the sympathetic nervous system and β‑adrenergic receptors. The study tested whether β‑adrenergic receptors are required for diet‑induced thermogenesis by generating mice lacking all three βARs. β‑less mice were created by knocking out the three known βAR genes, allowing comparison of metabolic rate and obesity on chow and high‑fat diets. β‑less mice displayed reduced metabolic rate and mild obesity on chow, but on a high‑fat diet they developed severe obesity due to impaired diet‑induced thermogenesis, confirming βARs are essential for this protective pathway.

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 β-adrenergic receptor (βAR) 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 βARs (β-less mice). β-less mice on a Chow diet had a reduced metabolic rate and were slightly obese. On a high-fat diet, β-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 βARs are necessary for diet-induced thermogenesis and that this efferent pathway plays a critical role in the body's defense against diet-induced obesity.