Oral Presentation ANZOS-Breakthrough Discoveries Joint Annual Scientific Meeting 2018

Role of amygdala NPY in the development of stress-induced obesity (#55)

Herbert Herzog 1
  1. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia

Neuropeptide Y (NPY) is one of the most powerful orexigenic peptides known, exerting critical feeding related functions in the hypothalamus. However, NPY is also present in extra hypothalamic nuclei where it is modulated in response to metabolic and other physiological perturbations, but far less is known about these NPY populations and their influence on energy homeostasis regulation. Now we have identified that NPY neurons in the central amygdala (CeA) are responsible for an exacerbated response to a combined stress and high fat diet intervention leading to accelerated obesity development. Employing CeA NPY neuron specific AAV-NPY overexpression models we were able to replicate the obese phenotype seen in the combined stress/HFD mouse model, which was prevented by the selective ablation of NPY from these neurons. Furthermore, by selectively activating NPY neurons of the CeA via DREADD we mapped the projections of these neurons to the Arc and PVN, known nuclei to be critical for energy homeostasis control. Moreover, using food intake and energy expenditure as the physiological readout we demonstrated that selective activation of CeA NPY neurons results in a robust increase in food intake and decrease in EE which is entirely dependent on the presence of NPY. Mechanistically it is the failure of insulin to no longer control these NPY neurons under combined stress/HFD conditions that leads to accelerated obesity. Taken together this study has uncovered a previously unknown feeding stimulatory pathway that is activated under conditions of stress in combination with calorie dense food.