Abstract
Ghrelin is a stomach-derived peptide hormone with salient roles in the regulation of energy balance and metabolism. Notably, ghrelin is recognized as the most powerful known circulating orexigenic hormone. Here, we systematically investigated the effects of ghrelin on energy homeostasis and found that ghrelin primarily induces a biphasic effect on food intake that has indirect consequences on energy expenditure and nutrient partitioning. We also found that ghrelin-induced biphasic effect on food intake requires the integrity of Agouti-related peptide/neuropeptide Y-producing neurons of the hypothalamic arcuate nucleus, which seem to display a long-lasting activation after a single systemic injection of ghrelin. Finally, we found that different autonomic, hormonal and metabolic satiation signals transiently counteract ghrelin-induced food intake. Based on our observations, we propose a heuristic model to describe how the orexigenic effect of ghrelin and the anorectic food intake-induced rebound sculpt a timely constrain feeding response to ghrelin.
Highlights
Ghrelin is an octanoylated peptide hormone synthesized in the stomach fundus that acts via the growth hormone secretagogue receptor (GHSR), which is mainly expressed in the brain
In order to test if the effects of ghrelin on EE and the respiratory exchange ratio (RER) were secondary to ghrelin-induced food intake, we investigated the effects of ghrelin on locomotor activity, EE and the RER in mice that were housed in calorimetric cages but were not allowed to eat after ghrelin treatment
We provide a compelling characterization of food intake, locomotor activity, EE and RER in mice systemically treated with ghrelin
Summary
Ghrelin is an octanoylated peptide hormone synthesized in the stomach fundus that acts via the growth hormone secretagogue receptor (GHSR), which is mainly expressed in the brain. The role of ghrelin becomes more evident in energy deficit conditions, such as calorie restriction or fasting, when plasma ghrelin levels increase and contribute to upregulate food seeking, food intake and hyperglycemic mechanisms [2, 3]. In this regard, ghrelin is recognized as the most powerful known orexigenic hormone. Injected ghrelin fails to induce food intake in mice with ablation of either the entire ARH or exclusively the ARHAgRP/NPY neurons [4, 12]. The putative effects of ghrelin on locomotor activity or EE are more controversial
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