Thalamic opioids from POMC satiety neurons switch on sugar appetite

• 成果类型: Article
• 署名作者: Minere, Marielle; Wilhelms, Hannah; Kuzmanovic, Bojana; Lundh, Sofia; Fusca, Debora; Classen, Alina; Shtiglitz, Stav; Prilutski, Yael; Talpir, Itay; Tian, Lin; Kieffer, Brigitte; Davis, Jon; Kloppenburg, Peter; Tittgemeyer, Marc; Livneh, Yoav; Fenselau, Henning
• 署名单位: University of Cologne; Novo Nordisk; University of Cologne; University of Cologne; Weizmann Institute of Science; Max Planck Society; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Lorraine; University of Cologne
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12809
• DOI: 10.1126/science.adp1510
• 发表日期: 2025-02-14
• 页码: 750-758
• 关键词: frameshift mutation; beta-endorphin; body-weight; food-intake; receptor; circuit; nucleus; reward; rat; hypothalamus

摘要

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.