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Cell Metab. 2019 Apr 25. pii: S1550-4131(19)30185-8. doi: 10.1016/j.cmet.2019.04.001. [Epub ahead of print]

Amygdala NPY Circuits Promote the Development of Accelerated Obesity under Chronic Stress Conditions.

Author information

1
Neuroscience Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia; Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia.
2
Neuroscience Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.
3
School of Biomedical Sciences & Pharmacy, University of Newcastle, Newcastle, NSW, Australia.
4
School of Psychology, University of New South Wales, Sydney, NSW 2052, Australia.
5
Max Planck Institute for Metabolism Research, Cologne, Germany.
6
Department of Pharmacology, Medical University Innsbruck, Innsbruck 6020, Austria.
7
Neuroscience Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia; Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: h.herzog@garvan.org.au.

Abstract

Neuropeptide Y (NPY) exerts a powerful orexigenic effect in the hypothalamus. However, extra-hypothalamic nuclei also produce NPY, but its influence on energy homeostasis is unclear. Here we uncover a previously unknown feeding stimulatory pathway that is activated under conditions of stress in combination with calorie-dense food; NPY neurons in the central amygdala are responsible for an exacerbated response to a combined stress and high-fat-diet intervention. Central amygdala NPY neuron-specific Npy overexpression mimics the obese phenotype seen in a combined stress and high-fat-diet model, which is prevented by the selective ablation of Npy. Using food intake and energy expenditure as readouts, we demonstrate that selective activation of central amygdala NPY neurons results in increased food intake and decreased energy expenditure. Mechanistically, it is the diminished insulin signaling capacity on central amygdala NPY neurons under combined stress and high-fat-diet conditions that leads to the exaggerated development of obesity.

KEYWORDS:

NPY; central amygdala; feeding; insulin; obesity; stress

PMID:
31031093
DOI:
10.1016/j.cmet.2019.04.001

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