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CNS beta(3)-adrenergic receptor activation regulates feeding behavior, white fat browning, and body weight

Journal article
Authors Jennifer E. Richard
Lorena López-Ferreras
Belén Chanclón
Kim Eerola
Peter Micallef
Karolina P Skibicka
Ingrid Wernstedt Asterholm
Published in American Journal of Physiology-Endocrinology and Metabolism
Volume 313
Issue 3
Pages E344-E358
ISSN 0193-1849
Publication year 2017
Published at Institute of Neuroscience and Physiology
Institute of Neuroscience and Physiology, Department of Physiology
Pages E344-E358
Language en
Keywords appetite regulation, adipose tissue browning, body weight, obesity, adipose-tissue thermogenesis, rat medulla-oblongata, energy-balance, food-intake, hypothalamic control, agonist, neurons, stimulation, expression, noradrenaline, Endocrinology & Metabolism, Physiology
Subject categories Clinical Medicine


Pharmacological beta(3)-adrenergic receptor (beta(3)AR) activation leads to increased mitochondrial biogenesis and activity in white adipose tissue (WAT), a process commonly referred to as "browning", and transiently increased insulin release. These effects are associated with improved metabolic function and weight loss. It is assumed that this impact of beta(3)AR agonists is mediated solely through activation of beta(3)ARs in adipose tissue. However, beta(3)ARs are also found in the brain, in areas such as the brain stem and the hypothalamus, which provide multisynaptic innervation to brown and white adipose depots. Thus, contrary to the current adipocentric view, the central nervous system (CNS) may also have the ability to regulate energy balance and metabolism through actions on central beta(3)ARs. Therefore, this study aimed to elucidate whether CNS beta(3)ARs can regulate browning of WAT and other aspects of metabolic regulation, such as food intake control and insulin release. We found that acute central injection of beta 3AR agonist potently reduced food intake, body weight, and increased hypothalamic neuronal activity in rats. Acute central beta(3)AR stimulation was also accompanied by a transient increase in circulating insulin levels. Moreover, subchronic central beta(3)AR agonist treatment led to a browning response in both inguinal (IWAT) and gonadal WAT (GWAT), along with reduced GWAT and increased BAT mass. In high-fat, high-sugar-fed rats, subchronic central beta(3)AR stimulation reduced body weight, chow, lard, and sucrose water intake, in addition to increasing browning of IWAT and GWAT. Collectively, our results identify the brain as a new site of action for the anorexic and browning impact of beta(3)AR activation.

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