Temporal control of eating and body weight by GHSR-expressing suprachiasmatic nucleus neurons

Food consumption impacts body weight differently depending on the time of day. Here, we investigated whether suprachiasmatic nucleus (SCN) neurons responsive to the hormone ghrelin temporally regulate eating and body weight in mice. The chemogenetic stimulation of GHSR (growth hormone secretagogue receptor)-expressing SCN neurons during the mid-rest phase-when mice are most sensitive to ghrelin's orexigenic effects-increased food intake. Repeated chemogenetic inhibition of these neurons during this same time of day reduced the corresponding, typically low amount of food intake; it also reduced the cumulative feed efficiency and body weight. These effects were not observed at other times of day. The chemogenetic stimulation of GHSR-expressing arcuate hypothalamic nucleus neurons increased food intake independently of time of day. GHSR-expressing SCN neurons represented subpopulations of six distinct SCN neuronal clusters, which were predominantly GABAergic and exhibited light-sensitive, time-of-day-dependent transcriptomic profiles. Thus, our study identifies GHSR-expressing SCN neurons as a neuronal population that regulates eating, feed efficiency, and body weight in a mid-rest phase-dependent manner.