Neuroendocrine Mediators, Food Intake and Obesity: A Narrative Review

Abstract

Obesity is a chronic multifactorial disease caused by imbalance between caloric intake and energy expenditure. The Neuroendocrine system is one of the main factors regulating energy intake in humans. The Neuroendocrine system is made up of cells able to synthesize and secrete amines, peptides, growth factors and biological mediators, known as neurohormones, which modulate various biological functions by interacting with the nervous and immune system. In the central nervous system, neurosecretory elements are mainly located in the hypothalamus which is the anatomical site of the hunger (lateral nucleus) and satiety (ventromedial nucleus) centers; thus it plays a key role in chemical coding of food intake. Dopamine, Noradrenaline and Serotonin are historically considered key points in the regulation of feeding behavior. However, other neurohormones have been identified; these substances, also synthesized in peripheral tissues (especially adipose tissue and digestive tract), influence food intake. Some of these hormones have orexigenic activity; conversely, other substances have anorexigenic activity. A constant balance between orexigenic and anorexigenic neurohormones is essential to ensure a smooth feeding behavior, whereas a subtle and progressive disruption of neurochemical transmission is sufficient to induce hyperphagia or anorexia. Several factors affect the synthesis and release of neuropeptides: genetic, hormonal, psychological, environmental, receptorial, type of feeding and meal frequency. In the recent past some drugs, as Sibutramine and Rimonabant, modulating the activity of several neuroendocrine mediators (Serotonin, Noradrenaline, Endocannabinoids), have proven to be effective in reducing weight excess, even if they were withdrawn because of serious side effects. Recently, promising results in this way have been obtained with Glucagon like Peptide-1 analogs, showing significant efficacy in counteracting weight excess without side effects. Further knowledge developments on these complex neuroendocrine circuits and their hypothalamic interactions in food intake regulation could open new frontiers for effective pharmacological therapeutic approach to Obesity and other nutritional disorders.