Critical role of lateral habenula circuits in the control of stress-induced palatable food consumption

Chi Kin Ip; Jemma Rezitis; Yue Qi; Nikita Bajaj; Julia Koller; Aitak Farzi; Yan-Chuan Shi; Ramon Tasan; Lei Zhang; Herbert Herzog

doi:10.1016/j.neuron.2023.05.010

Critical role of lateral habenula circuits in the control of stress-induced palatable food consumption

Neuron. 2023 Aug 16;111(16):2583-2600.e6. doi: 10.1016/j.neuron.2023.05.010. Epub 2023 Jun 8.

Authors

Chi Kin Ip¹, Jemma Rezitis², Yue Qi², Nikita Bajaj², Julia Koller², Aitak Farzi³, Yan-Chuan Shi⁴, Ramon Tasan⁵, Lei Zhang⁶, Herbert Herzog⁷

Affiliations

¹ Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia; Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: k.ip@garvan.org.au.
² Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
³ Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, 8010 Graz, Austria.
⁴ Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia; Neuroendocrinology Group, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
⁵ Department of Pharmacology, Medical University Innsbruck, 6020 Innsbruck, Austria.
⁶ Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia; Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia.
⁷ Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia; Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: h.herzog@garvan.org.au.

PMID: 37295418
DOI: 10.1016/j.neuron.2023.05.010

Abstract

Chronic stress fuels the consumption of palatable food and can enhance obesity development. While stress- and feeding-controlling pathways have been identified, how stress-induced feeding is orchestrated remains unknown. Here, we identify lateral habenula (LHb) Npy1r-expressing neurons as the critical node for promoting hedonic feeding under stress, since lack of Npy1r in these neurons alleviates the obesifying effects caused by combined stress and high fat feeding (HFDS) in mice. Mechanistically, this is due to a circuit originating from central amygdala NPY neurons, with the upregulation of NPY induced by HFDS initiating a dual inhibitory effect via Npy1r signaling onto LHb and lateral hypothalamus neurons, thereby reducing the homeostatic satiety effect through action on the downstream ventral tegmental area. Together, these results identify LHb-Npy1r neurons as a critical node to adapt the response to chronic stress by driving palatable food intake in an attempt to overcome the negative valence of stress.

Keywords: DREADD; Npy; Npy1r; TRAP sequencing; lateral habenula; obesity; optogenetics; palatable food intake; stress.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Habenula* / physiology
Hypothalamic Area, Lateral
Mice
Neural Pathways / physiology
Neurons / physiology
Ventral Tegmental Area