Early on, corticotropin-releasing factor (CRF), a hallmark brain peptide mediating many components of the stress response, was shown to affect food intake inducing a robust anorexigenic response when injected into the rodent brain. Subsequently, other members of the CRF signaling family have been identified, namely urocortin (Ucn) 1, Ucn 2 and Ucn 3 which were also shown to decrease food intake upon central or peripheral injection. However, the kinetics of feeding suppression was different with an early decrease following intracerebroventricular injection of CRF and a delayed action of Ucns contrasting with the early onset after systemic injection. CRF and Ucns bind to two distinct G-protein coupled membrane receptors, the CRF1 and CRF2. New pharmacological tools such as highly selective peptide CRF1 or CRF2 agonists or antagonists along with genetic knock-in or knock-out models have allowed delineating the primary role of CRF2 involved in the anorexic response to exogenous administration of CRF and Ucns. Several stressors trigger behavioral changes including suppression of feeding behavior which are mediated by brain CRF receptor activation. The present review will highlight the state-of-knowledge on the effects and mechanisms of action of CRF/Ucns-CRF1/2 signaling under basal conditions and the role in the alterations of food intake in response to stress.

Bile acids may be involved in the regulation of food intake and energy metabolism. The aim of the study was to investigate the association of plasma bile acids with body mass index (BMI) and the possible involvement of circulating bile acids in the modulation of physical activity and eating behavior. Blood was obtained in a group of hospitalized patients with normal weight (BMI 18.5-25 kg/m2), underweight (anorexia nervosa, BMI 50 kg/m2, n=14-15/group) and plasma bile acid concentrations assessed. Physical activity and plasma bile acids were measured in a group of patients with anorexia nervosa (BMI 14.6±0.3 kg/m2, n=43). Lastly, in a population of obese patients (BMI 48.5±0.9 kg/m2, n=85), psychometric parameters related to disordered eating and plasma bile acids were assessed. Plasma bile acids showed a positive correlation with BMI (r=0.26, p=0.03) in the population of patients with broad range of BMI (9-85 kg/m2, n=74). No associations were observed between plasma bile acids and different parameters of physical activity in anorexic patients (p>0.05). Plasma bile acids were negatively correlated with cognitive restraint of eating (r=-0.30, p=0.008), while no associations were observed with other psychometric eating behavior-related parameters (p>0.05) in obese patients. In conclusion, these data may point towards a role of bile acids in the regulation of body weight. Since plasma bile acids are negatively correlated with the cognitive restraint of eating in obese patients, this may represent a compensatory adaptation to prevent further overeating.

This review focuses on the control of appetite by food intake-regulatory peptides secreted from the gastrointestinal tract, namely cholecystokinin, glucagon-like peptide 1, peptide YY, ghrelin, and the recently discovered nesfatin-1 via the gut-brain axis. Additionally, we describe the impact of external factors such as intake of different nutrients or stress on the secretion of gastrointestinal peptides. Finally, we highlight possible conservative-physical activity and pharmacotherapy-treatment strategies for obesity as well as surgical techniques such as deep brain stimulation and bariatric surgery also altering these peptidergic pathways.