Physiologic and molecular determinant of brain susceptibility to reward- and metabolic-based diseases – BrainHealth

Obesity has reached a pandemic level and there is an urge to identify vulnerability/protective factors. Evidence support that obesity results from an interaction between genes and food environment. the TaqI A1 single nucleotide polymorphism is widely present in the population and has been identified as a main genetic vulnerability factor for both obesity and addictive & compulsive behavior. Our established that the influence of nutritional lipid on brain’ reward structures depends on TaqIA polymorphism in human. TaqIA is located in the gene that codes for the Ankyrin repeat and kinase domain containing 1 kinase (Ankk1), which function is unknown. Using a unique mouse model, we found that Ankk1 loss-of-function in brain reward structures leads to behavioral and metabolic defect similar to those described in human A1 carrier. We therefore make the hypothesis that Ankk1 is a molecular hub connecting diet and brain susceptibility/resilience to develop reward- and metabolic-based diseases.