AgRP neurons are not indispensable for body weight maintenance in adult mice

In addition to their role in promoting feeding and obesity development, hypothalamic arcuate agouti-related protein/neuropeptide Y (AgRP/NPY) neurons are widely perceived to be indispensable for maintaining normal feeding and body weight in adults, and consistently, acute inhibition of AgRP neurons is known to reduce short-term food intake. Here, we adopted complementary methods to achieve nearly complete ablation of arcuate AgRP/NPY neurons in adult mice and report that lesioning arcuate AgRP/NPY neurons in adult mice causes no apparent alterations in ad libitum feeding or body weight. Consistent with previous studies, loss of AgRP/NPY neurons blunts fasting refeeding. Thus, our studies show that AgRP/NPY neurons are not required for maintaining ad libitum feeding or body weight homeostasis in adult mice. [Display omitted] •AgRP neurons were selectively ablated in adult mice with DTX (i.c.v.) or AAV caspase-3•Ablation of AgRP neurons in adult mice does not affect normal feeding and body weight•Ablation of AgRP neurons blunts fasting refeeding Cai et al. find that ablation of AgRP neurons does not disrupt ad libitum feeding or body weight in adult mice, which argues against a necessary role of AgRP neurons for normal feeding or body weight. This study highlights the need for further research on AgRP neurons, particularly in more natural contexts.