Thalamic opioids from POMC satiety neurons switch on sugar appetite
High sugar-containing foods are readily consumed, even after meals and beyond fullness sensation (e.g., as desserts). Although reward-driven processing of palatable foods can promote overeating, the neurobiological mechanisms that underlie the selective appetite for sugar in states of satiety remain unclear. Hypothalamic pro-opiomelanocortin (POMC) neurons are principal regulators of satiety because they decrease food intake through excitatory melanocortin neuropeptides. We discovered that POMC neurons not only promote satiety in fed conditions but concomitantly switch on sugar appetite, which drives overconsumption. POMC neuron projections to the paraventricular thalamus selectively inhibited postsynaptic neurons through mu-opioid receptor signaling. This opioid circuit was strongly activated during sugar consumption, which was most notable in satiety states. Correspondingly, inhibiting its activity diminished high-sugar diet intake in sated mice.
Authors
- Peter Kloppenburg (ORCID: https://orcid.org/0000-0002-4554-404X)
- Sofia Lundh (ORCID: https://orcid.org/0000-0002-4552-0312)
- Yael Prilutski (ORCID: https://orcid.org/0000-0002-5086-0506)
- Stav Shtiglitz (ORCID: https://orcid.org/0009-0006-4915-706X)
- Marc Tittgemeyer (ORCID: https://orcid.org/0000-0001-5072-2149)
- Brigitte L. Kieffer (ORCID: https://orcid.org/0000-0002-8809-8334)
- Yoav Livneh (ORCID: https://orcid.org/0000-0002-0434-4201)
- Marielle Minère (ORCID: https://orcid.org/0000-0001-7889-9771)
- Bojana Kuzmanovic (ORCID: https://orcid.org/0000-0002-3698-7789)
- Debora Fuscà (ORCID: https://orcid.org/0000-0001-6089-8228)
- Jon F. Davis (ORCID: https://orcid.org/0000-0002-8859-2834)
- Hannah Wilhelms (ORCID: https://orcid.org/0000-0002-4508-7942)
- Lin Tian (ORCID: https://orcid.org/0000-0001-7012-6926)
- Henning Fenselau (ORCID: https://orcid.org/0000-0001-7136-9751)
- Itay Talpir (ORCID: https://orcid.org/0009-0009-4749-9324)
- A. Claßen
Institutions
- Inserm (FR)
- University of Cologne (DE)
- Novo Nordisk (Denmark) (DK)
- Max Planck Institute for Metabolism Research (DE)
- Max Planck Florida Institute for Neuroscience (US)
- Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE)
- Novo Nordisk (Germany) (DE)
- University Hospital Cologne (DE)
- Weizmann Institute of Science (IL)
- Université de Strasbourg (FR)
Publication Details
- Journal
- Science
- Published
- 2025-02-13
- DOI
- https://doi.org/10.1126/science.adp1510
- Citations
- 20
- Primary Topic
- Regulation of Appetite and Obesity
- Type
- article
- Field-Weighted Citation Impact
- 18.29