Metabolic Changes Induced by Purinergic Signaling: Role in Food Intake

Abstract

The purinergic signalling has a well-established role in the regulation of energy homeostasis, but there is growing evidence of its implication in the control of food intake. In this review, we provide an integrative view of the molecular mechanisms leading to changes in feeding behaviour within hypothalamic neurons following purinergic receptor activation. We also highlight the importance of purinergic signalling in metabolic homeostasis and the possibility of targeting its receptors for therapeutic purposes.

Keywords: food intake; metabolic homeostasis; obesity; orexigen and anorexigen neurons; purinergic receptors.

FIGURE 1

Schematic representation of purinergic signalling in hypothalamus. In the hypothalamus, purinergic signalling is involved in several complex aspects regulating food intake. Endogenous appetite stimulants such as ghrelin promotes food intake inactivating the anorexigenic proopiomelanocortin (POMC) neurons activity, while leptin inhibits the orexogenic signalling of AgRP/NPY neurons. Purinergic receptors are abundantly expressed in the ARC, paraventricular nucleus (PVN), lateral hypothalamus (LH). Strong P2X2R immunoreactivity is found in cell bodies of orexigenic NPY/AGRP/GABA neurons in the ARC and only occasionally in cell bodies of neurons expressing anorexigenic peptides. AgRP neurons also express UDP-activated P2Y6R. The ventromedial (VMH) and lateral hypothalamus (LH) are brain regions with antagonistic functions in the regulation of food intake in which activation of VMH neurons inhibits feeding, whereas stimulation of LH neurons enhances food intake. Peripheral stimulation of purinergic receptors in brown adipose tissue, pancreatic β-cells or taste buds regulates the circulating levels of leptin, insulin and other factors involved in food intake. Stimulation of A2A/A2B receptors induces browning of adipose tissue that in turn increases thermogenesis thus preventing fat accumulation.