betaAR signaling required for diet-induced thermogenesis and obesity resistance.
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.
Bachman
Eric S
ES
Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, 99 Brookline Avenue, Boston, MA 02215, USA.
Dhillon
Harveen
H
Zhang
Chen-Yu
CY
Cinti
Saverio
S
Bianco
Antonio C
AC
Kobilka
Brian K
BK
Lowell
Bradford B
BB
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001481:Basal Metabolism / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology; D002149:Energy Intake; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D010101:Oxygen Consumption / Q000187:drug effects; D010641:Phenotype; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D022722:Thermogenesis / Q000235:genetics / Q000502:physiology*
D004041:Dietary Fats; D011943:Receptors, Adrenergic, beta