How does the central nervous system integrate hunger and satiety?
A study by Cheung and colleagues reported in this issue of the JCI (4) provides a quantum increase in our understanding of CKD-associated anorexia. Using animal models of CKD, the authors uncovered defects in the complex neuroendocrine pathways that regulate food intake. To appreciate the scope of their studies, a brief background is needed (see Figure 1). For over 50 years, it has been recognized that inhibitory signals proportional to body fat stores act to decrease food intake (5). The so-called long-term regulators of appetite — insulin and leptin — are produced in the pancreas and adipose cells, respectively. These regulators circulate at levels proportional to body fat and enter the brain in proportion to their plasma levels. In the hypothalamus, they influence neural pathways that integrate feeding and satiety as well as energy expenditure (6, 7). High levels of either leptin or insulin decrease food intake and increase energy expenditure, while low levels stimulate appetite and
