The role of opioid peptides in eating behaviours and obesity

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Numerous demographic reports over the last two decades described a worldwide increase in the percentage of obese and overweight people and, consequently, a tremendous rise of obesity-related health problems. The problem is still increasing, even though many overweight individuals attempt to control their diet in view of the adverse health consequences and also because most people consider a lean and fit body to be more desirable. Many investigators have noted commonalities between an uncontrolled intake of food and drug addiction, including specific behaviours, neuronal circuits and neurotransmitter systems. Most importantly, the loss of control over eating behaviours and a compulsive food intake observed in some obese individuals bears a resemblance to compulsive drug taking behaviours in people suffering from drug dependence. Several neurotransmitter and neuromodulatory systems have been described that are critically involved in these processes, such as the dopaminergic system, the endocannabinoid system, or the opioid system. The focus of this proposal is on the endogenous opioid system, which is a critical regulator of hedonic responses. The involvement of the opioid peptides in food preference and in the executive control of eating behaviour was shown in some studies, but the exact mechanisms underlying these observations are still discussed. Thus, human and animal studies for example revealed that impulsivity is associated with opiate addiction, but it is not entirely clear if this is cause or consequence of the addiction process. Similarly, executive control dysfunctions have also been implicated in eating disorders, such as anorexia and bulimia nervosa, as well as obesity. In previous studies we investigated the function of opioid peptides in the modulation of animal behaviours. We generated mice deficient for the opioid peptides enkephalin and dynorphin showed that these peptides have a profound effect on drug reward and addiction, emotionality, stress-responses and nociception. The main hypothesis of this proposal is that a prolonged voluntary consumption of high caloric palatable food, leading to obesity, produces alterations in opioid signalling. These alterations in turn impact on hedonic aspects and executive control of food intake. To test this hypothesis we will use a combination of behavioural and molecular studies in animals with genetically disrupted opioid signalling. We aim to clarify the role of specific components of the endogenous opioid system in the regulation of food intake in lean and obese subjects. A particular emphasis will be placed on obesity-induced changes in the incentive salience of food rewards and executive control functions.