NIH Research Festival
Hunger and satiety are regulated, to a major extent, by the agouti related protein (AgRP)/neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons residing in the arcuate nucleus of the hypothalamus. During starvation, AgRP neurons are strongly activated to promote hunger. Peripheral hormones and nutrients regulate the function of AgRP neurons, thus ensuring proper glucose and energy homeostasis. Recent studies from various labs, including our group, have shown the importance of G-protein coupled receptors (GPCRs) in regulating the activity of AgRP neurons. GPCR function is modulated by a pair of proteins known as beta-arrestin-1 and -2 ( barr1 and barr2, respectively), which can terminate GPCR signaling and/or mediate GPCR-independent signaling. It is well established that barr1 and barr2 are involved in various physiological functions. However, the potential roles of barr1 and barr2 in regulating the function of AgRP neurons remain unexplored. To address this issue, we generated mice that lack barr1 or barr2 selectively in AgRP neurons using Cre/loxP-flex-switch technology. Interestingly, AgRP-barr1-KO mice consuming a high fat diet showed impaired glucose tolerance and insulin sensitivity, while body weight and food intake remained unchanged. Moreover, blood glucose and plasma insulin levels were increased in AgRP-barr1-KO mice. In contrast, AgRP-barr2-KO mice showed no obvious metabolic phenotypes. More detailed studies into the mechanisms through which barr1 regulates the activity of AgRP neurons may lead to new strategies to alter the activity of this class of neurons for therapeutic purposes.
Scientific Focus Area: Neuroscience
This page was last updated on Friday, March 26, 2021