Regulation of energy balance and body weight by the brain: a distributed system prone to disruption

Abstract

Maintaining adequate energy supply via regulation of food intake and energy expenditure is crucial for survival and reproduction. The neural control of energy balance is highly complex, occurs across distributed central and peripheral areas, and incorporates multiple domains of control (including homeostatic and hedonic processes). The sheer number of active compounds (such as leptin and GLP-1) involved in the regulation of food intake speaks to the redundancy and complexity of the system. The balance between energy intake and expenditure is under CNS control. Constant bidirectional communication between the brain and the GI tract, as well as between the brain and other relevant tissues (ie, adipose tissue, pancreas, and liver), ensures that the brain constantly perceives and responds accordingly to the energy status/needs of the body. This elegant biological system is subject to disruption by a toxic obesogenic environment, leading to syndromes such as leptin and insulin resistance, and ultimately further exposing obese individuals to further weight gain and T2DM. Recent imaging studies in humans are beginning to examine the influence that higher-order/hedonic brain regions have on homeostatic areas, as well as their responsiveness to homeostatic peripheral signals. With greater understanding of these mechanisms, the field moves closer to understanding and eventually treating the causalities of obesity.

Figure 1

The distributed CNS nuclei control energy intake. The circulating energy-status signals, as well as vagally-mediated satiation signals, can act either directly or indirectly on both homeostatic nuclei (hypothalamus and nucleus tractus solitarius [NTS] in the brainstem) and hedonic/non-homeostatic nuclei.