An important goal in metabolism is to identify brain regions capable of regulating energy balance. These brain regions represent potential druggable targets for the modification of food intake and energy expenditure, which could help to combat any number of debilitating disorders relating to metabolic function and body weight. We have recently identified the dorsal raphe nucleus (DRN) as a key node in the central nervous system regulating both food intake and energy expenditure. In particular, we have found that inhibitory, GABAergic neurons residing in the dorsolateral aspect of this nucleus are activated by hunger and in turn induce the appropriate counterregulatory responses – namely, to increase food intake and suppress energy expenditure. Here, using a combination of ensemble-level molecular profiling in tandem with single-nuclear RNA sequencing, we demonstrate that these GABAergic neurons are molecularly heterogeneous and express a host of factors directly implicated in the central control of energy homeostasis. Of note, a few of these subpopulations express abundant levels of transcript for neuropeptides important in regulating energy balance, such as thyrotropin-releasing hormone (Trh) and neuropeptide Y (Npy). These profiling studies thus demonstrate a previously underappreciated level of heterogeneity within GABAergic neurons of the DRN suggesting a multifaceted, and possibly distributed, mechanism through which these neurons may regulate energy balance. Together, this work molecularly characterizes the DRN at a resolution not previously possible and identifies cell subpopulations through which this nucleus may regulate energy homeostasis.
V.M. Bhave: None. N. Kamatkar: None. A.R. Nectow: None.
American Diabetes Association/Pathway to Stop Diabetes (1-18-ACE-49 to A.R.N.); American Diabetes Association (1-18-IBS-148 to A.R.N.); Foundation for Prader-Willi Research; National Alliance for Research on Schizophrenia & Depression