CRC/Transregio TRR 134: Ingestive Behaviour: Homeostasis and Reward

The incidence and prevalence of obesity continues to rise and is particularly observed in populations that are exposed to an unprecedented abundance of food. Against this background, it represents an urgent task to unravel the central nervous mechanisms that act to integrate the homeostatic and reward-associated neurocircuits encoding the behavioural portfolio relevant for food choice and intake. Based on the significant and exciting progress made in the first funding period, we will now expand our conceptual approach and efforts to systematically move towards a more system-based and translational research programme. To this end, we will position our goal to decipher the interaction between homeostatic and reward circuits in a broader context with regards to neuronal and functional interactions (level A). The analysis of this crosstalk will also include relevant models of social interaction and cue triggered/external eating behaviour in a more clinically oriented translational context (level B). Clearly defined intervention strategies to enable tackling these problems through neuromodulation, pharmacological means or targeted neurosurgical approaches will be employed (level C). Finally, human studies within the T-CRC will now benefit from a pheno- and genotypically well-characterized cohort in the Z2 project. The recruitment of normal individuals and individuals which are environmentally or genetically prone to altered eating behaviour is clearly essential for the experimental paradigms and targeted interventions of the next funding period.

The incidence and prevalence of obesity continues to rise and is particularly observed in populations exposed to an unprecedented abundance of food. Against this background, it represents an urgent task to unravel the central nervous mechanisms that act to integrate the homeostatic and rewardassociated neurocircuits encoding the behavioural portfolio relevant for food choice and intake. Consequently, it will be mandatory to search for an altered convergence of these two systems as the underlying basis for disturbed eating behaviour. To this end, we have defined fundamental principles of dysfunction in the pathogenesis of homeostatic versus reward driven obesity, namely (i) a disturbed processing of sensory signals, (ii) the loss of physiological function of satiety signals in the homeostatic system, (iii) a disturbed communication between reward and homeostatic systems with either insufficient inhibition of reward signals by homeostatic mechanisms or disinhibition of homeostatic signals by reward-associated stimulation and (iv) the tendency of reward-triggered food intake to eventually evolve into habitual behaviour. Within this concept, we have systematically moved towards a more system-based and translational research programme to decipher the interaction between homeostatic and reward circuits in a broader context with regards to neuronal and functional interactions (level A). The analysis of this crosstalk has also included relevant models of social interaction and cue triggered/external eating behaviour in a more clinically oriented translational context (level B). Clearly defined intervention strategies to enable tackling these problems through neuromodulation, pharmacological means or targeted neurosurgical approaches have been employed (level C). Finally, human studies within the CRC have benefitted from a pheno- and genotypically well-characterized cohort in the Z2 project. The recruitment of normal individuals and individuals which are environmentally or genetically prone to altered eating behaviour is clearly essential for the experimental paradigms and targeted interventions within this program. We anticipate conceptual advances for the whole research area in a long-term perspective. Based on the novel and mechanistic insight into the principles of convergence and regulation of the homeostatic and reward systems, thorough insight into the association between specific behavioural patterns and neural signals will be gained and will, by the aid of the cohort established, move our approaches towards a more targeted and precision medicine approach, which is needed for the treatment of obese persons. This CRC was (and with its scientific offsprings continues to be) embedded into a strong and focused research infrastructure at the participating universities and has received highest priority in terms of strategic planning and support. Moreover, the participating scientists have created a consortial and highly cooperative environment that will continue to build upon the complementary strengths and the joint and well-defined research focus.