Hypothalamic and brainstem neuronal circuits controlling homeostatic energy balance

Abstract

Alterations in adequate energy balance maintenance result in serious metabolic disturbances such as obesity. In mammals, this complex process is orchestrated by multiple and distributed neuronal circuits. Hypothalamic and brainstem neuronal circuits are critically involved in the sensing of circulating and local factors conveying information about the energy status of the organism. The integration of these signals culminates in the generation of specific and coordinated physiological responses aimed at regulating energy balance through the modulation of appetite and energy expenditure. In this article, we review current knowledge on the homeostatic regulation of energy balance, emphasizing recent advances in mouse genetics, electrophysiology, and optogenetic techniques that have greatly contributed to improving our understanding of this central process.

Hypothalamo-gastrointestinal axis – role in food intake regulation

“…The NPY expression and release is related to changes in the organism energy status. NPY activity is reduced under feeding conditions, whereas the malnutrition stimulates its activity (Schneeberger et al, 2014). Moreover, intracerebroventricular (ICV) administration of NPY or its direct administration into specific hypothalamic nuclei increases food intake, whereas the administration of receptor selective antagonists (Y1 and Y5 antagonists) or antisense oligonucleotides (Y5 receptor) reduces or inhibits food intake (Lopaschuk et al, 2010).…”

“…Similar to NPY, the expression of AgRP is elevated during fasting and/or malnutrition conditions. On the other hand, the central administration of AgRP stimulates food intake and reduces energy expenditure resulting in increased obesity (Schneeberger et al, 2014).…”

“…CART's expression is increased under feeding conditions, particularly as a consequence of the high-energy/high-fat food consumption (Wortley et al, 2004), and decreased under fasting conditions (Robson et al, 2002). Moreover, ICV infusion of CART results in the appetite reduction, while antibodies against CART reverse this effect (Schneeberger et al, 2014). It has been demonstrated, that polymorphisms of the gene, as well as alterations in CART protein level, are associated with human obesity (Lopaschuk et al, 2010).…”

“…The central administration of orexins not only increases food intake, but also promotes behavioural responses to food reward and increases arousal (Cason et al, 2010). NPY, AgRP and -MSH terminals project into the LHA and contact with melaninconcentrating hormone (MCH) or orexin expressing cells, in turn, central orexin neurons express NPY and leptin receptors and are thus able to integrate adiposity signals (Schneeberger et al, 2014).…”

“…Ghrelin is another modulator of energy balance, with crucial role in appetite regulation, fuel substrate preference, body weight and glucose homeostasis. It is worth emphasizing, that ghrelin, in contrary to many other peripheral hormones, exhibits a powerful orexigenic actions (Schneeberger et al, 2014). Thereby, the level of ghrelin in plasma is reduced after the meal.…”