Ghrelin, peptide YY and their hypothalamic targets differentially regulate spontaneous physical activity

Recent studies suggest that spontaneous physical activity (SPA) may be under the non-conscious control of neuroendocrine circuits that are known to control food intake. To further elucidate endocrine gut–brain communication as a component of such circuitry, we here analyzed long-term and acute effects of the gastrointestinal hormones ghrelin and PYY 3-36 as well as their hypothalamic neuropeptide targets NPY, AgRP and POMC (alpha-MSH), on locomotor activity and home cage behaviors in rats. For the analysis of SPA, we used an automated infrared beam break activity measuring system, combined with a novel automated video-based behavior analysis system (HomeCageScan (HCS)).Chronic (one-month) peripheral infusion of ghrelin potently increased body weight and fat mass in rats. Such positive energy balance was intriguingly not due to an overall increased caloric ingestion, but was predominantly associated with a decrease in SPA. Chronic intracerebroventricular infusion (7 days) of ghrelin corroborated the decrease in SPA and suggested a centrally mediated mechanism. Central administration of AgRP and NPY increased food intake as expected. AgRP administration led to a delayed decrease in SPA, while NPY acutely (but transiently) increased SPA. Behavioral dissection using HCS corroborated the observed acute and transient increases of food intake and SPA by central NPY infusion. Acute central administration of alpha-MSH rapidly decreased food intake but did not change SPA. Central administration of the NPY receptor agonist PYY 3-36 transiently increased SPA.Our data suggest that the control of spontaneous physical activity by gut hormones or their neuropeptide targets may represent an important mechanistic component of energy balance regulation.

Research Highlights
► Endocrine gut-brain communications control spontaneous physical activity (SPA).
► Chronic ghrelin infusion increases body weight and fat mass, but decreases SPA.
► Acute central infusion of AGRP decreases SPA, PYY 3-36 and NPY increase SPA.
► Acute central infusion of alpha-MSH decreases food intake but does not change SPA.
► The direct (neuro)endocrine control of SPA is important for energy balance regulation.