Another way to understand how animals change their feeding behavior is to examine the neurochemical regulation of increased appetite. The essential question of this research is, why do we feel hungry when the body’s store of calories runs low? How does the brain know that body fat is decreasing during a prolonged fast? How are the signals of caloric deficit converted to food-seeking behaviors? Conversely, after eating a meal, how does the brain know to stop eating long before the food is absorbed from the gut and the calories appear in the blood? As with conditioned taste aversion, the ability to monitor caloric need and generate hunger signals is critical for survival, and animals are "hard-wired" to respond.
My particular focus has been on the role of neuropeptides in the hypothalamus of the brain. The hypothalamus is an integrative center of the brain, receiving hormonal and neural input from the body and the environment. Much as a thermostat maintains temperature, the hypothalamus then produces behavioral and physiological responses to maintain a constant internal environment for proper body functions. In particular, the hypothalamus is critical for responding to long-term changes in body weight and caloric balance by increasing or decreasing food intake. In other words, the hypothalamus makes rats and humans feel hungry or satiated.
Neuropeptides are very small proteins that are encoded by genes. Unlike the large structural proteins that form the physical connections between brain cells, neuropeptides are small enough to serve as chemical messengers between neurons, or between the fat depots of the body and the brain. The fat hormone leptin is an example of a neuropeptide that is secreted from fat cells into the blood, and signals the brain (via the hypothalamus) that caloric storage is high. During starvation or chronic food restriction, fat is used up, the fat cells cease to secrete leptin, and leptin levels in the blood fall. The hypothalamus detects the drop in leptin, interprets the low leptin as a lack of calories, and generates the sensation of hunger (observed in the rats as increased appetitive behaviors).
The goal of my research has been to characterize the neuropeptides that the hypothalamus uses to generate hunger and satiety in response to leptin or its absence. There are many different neuropeptides used as chemical signals in the circuits of the hypothalamus, and each may play a subtly different role in the response to caloric deficiency. For example, we have compared two neuropeptides involved in hunger. Both "Neuropeptide Y" (NPY) and "Agouti-gene-related peptide" (AGRP) appear to signal hunger. When a rat is food-deprived, levels of NPY and AGRP are increased in the brain. If NPY or AGRP are injected into a satiated rat, the rat becomes ravenously hungry. However, NPY and AGRP have different temporal characteristics. NPY levels increase rapidly with food deprivation, and NPY injections induced feeding for only a few minutes. AGRP, on the other hand, is slow to rise during fasting and slow to fall upon refeeding; a single injection of AGRP will cause a rat to overeat for several days.
The cellular mechanisms and the circuitry underlying these differences are largely unknown. My collaborators and I have employed pharmacological treatments (Rushing and Houpt 1999; Jahng and Houpt 2001; Eckel et al. 2002), and mutant rodent models of obesity and anorexia (Kowalski et al. 1999, Nardos et al. submitted), and food restriction ((Swart et al. 2001, 2002, and submitted) to probe the regulation of feeding. This research is significant because it examines the underlying brain neurochemicals that mediate appetite, both in human obesity (pathological overeating) and in human eating disorders (pathological undereating).
© 2014 T.A. Houpt. Last updated 2014-10-17.