Chronic G <sub>q</sub> signaling in AgRP neurons does not cause obesity
Sedona N. Ewbank, Carlos Campos, Jane Chen, Anna J. Bowen, Stéphanie L. Padilla, Joseph L. Dempsey, Julia Yue Cui, Richard D. Palmiter
Abstract
Significance Mammals maintain energy homeostasis and a stable body weight via neural circuits that regulate food intake and metabolism. Understanding how signaling within these circuits influences feeding, metabolism, and body weight is critical for understanding and treating diseases involving altered energy homeostasis, such as obesity and cachexia. Hypothalamic AgRP-expressing neurons are known to induce hyperphagia and decrease energy expenditure when acutely activated; however, the effects of chronic hyperactivity in AgRP neurons—which occurs in obese individuals—are unknown. Here, we show that chronic G q -mediated activation of AgRP neurons in mice does not cause long-lasting obesogenic changes in feeding, body weight, gut microbiome, or energy expenditure, but does cause increased adiposity and increased lipid metabolism, even under caloric restriction.