BackgroundThe gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism.Scope of reviewIn this review, we discuss the diverse biological functions of ghrelin, the regulation of its secretion, and address questions that still remain 15 years after its discovery.Major conclusionsIn recent years, ghrelin has been found to have a plethora of central and peripheral actions in distinct areas including learning and memory, gut motility and gastric acid secretion, sleep/wake rhythm, reward seeking behavior, taste sensation and glucose metabolism.

IntroductIonOne-third of the US population is clinically obese (BMI ≥30 kg/m 2 ) (1), a condition associated with increased morbidity and health-care costs (2). Although the origins of this problem are complex, caloric intake in excess of expenditure is the primary cause of weight gain. Food intake is influenced by a convergence of processes in the brain, including homeostatic mechanisms, motivation, cognitive control, and decision making (3). Research has shown that obese individuals find food more reinforcing compared to healthy weight (HW) individuals (4,5). The motivational value of food can be measured by determining the extent to which an individual will work to obtain food (3) and is influenced by a variety of factors including food composition (6,7) and hunger (3).In experimental settings, obese individuals show increased food motivation, compared to HW individuals, by working more for food rewards than nonfood rewards (4) and by consuming more food in laboratory settings than individuals who demonstrate lower levels of food motivation (4,8). In addition, obese individuals, compared to overweight and HW individuals, report higher levels of eating disinhibition and hunger on the Three Factor Eating Inventory (EI) (9), which measures dietary restraint (conscious effort to control dietary intake), eating disinhibition (release of control under emotional or situational triggers), and hunger (feeling hunger and its relationship to eating) (10).Functional neuroimaging studies are beginning to examine brain mechanisms underlying food motivation. Positron emission tomography studies in HW adults, examining brain activations during food consumption, show changes in regional cerebral blood flow (rCBF) in prefrontal regions, including ventromedial prefrontal cortex (PFC), as well as insular cortical regions (11)(12)(13)(14)(15). In these studies, researchers manipulated food motivation by increasing participant hunger through fasting (4.5-36 h) and measuring responses to a liquid meal (11-13,15) or chocolate (14). rCBF increased during hungry states in the hypothalamus, insula, and the orbitofrontal cortex (11,14,15). Meal consumption was associated with increased rCBF in prefrontal regions such as the ventromedial PFC (11,13,15). It should be noted that re-analysis of rCBF results (11,13,15) using a random effects as opposed to fixed effects analysis revealed decreases rather than increases in dorsolateral prefrontal regions (16,17). One out of three adults in the United States is clinically obese. Excess food intake is associated with food motivation, which has been found to be higher in obese compared to healthy weight (HW) individuals. Little is known, however, regarding the neural mechanisms associated with food motivation in obese compared to HW adults. The current study used functional magnetic resonance imaging (fMRI) to examine changes in the hemodynamic response in obese and HW adults while they viewed food and nonfood images in premeal and postmeal states. During the premeal condition, obese participants...

Objective: To investigate the neural mechanisms of food motivation in children and adolescents, and examine brain activation differences between healthy weight (HW) and obese participants. Subjects: Ten HW children (ages 11-16; BMI o 85%ile) and 10 obese children (ages 10-17; BMI 495%ile) matched for age, gender and years of education. Measurements: Functional magnetic resonance imaging (fMRI) scans were conducted twice: when participants were hungry (pre-meal) and immediately after a standardized meal (post-meal). During the fMRI scans, the participants passively viewed blocked images of food, non-food (animals) and blurred baseline control. Results: Both groups of children showed brain activation to food images in the limbic and paralimbic regions (PFC/OFC). The obese group showed significantly greater activation to food pictures in the PFC (pre-meal) and OFC (post-meal) than the HW group. In addition, the obese group showed less post-meal reduction of activation (vs pre-meal) in the PFC, limbic and the reward-processing regions, including the nucleus accumbens. Conclusion: Limbic and paralimbic activation in high food motivation states was noted in both groups of participants. However, obese children were hyper-responsive to food stimuli as compared with HW children. In addition, unlike HW children, brain activations in response to food stimuli in obese children failed to diminish significantly after eating. This study provides initial evidence that obesity, even among children, is associated with abnormalities in neural networks involved in food motivation, and that the origins of neural circuitry dysfunction associated with obesity may begin early in life.