Opioidergic signaling contributes to food-mediated suppression of AgRP neurons


Sayar-Atasoy N., Yavuz Y., Laule C., Dong C., Kim H., Rysted J., ...Daha Fazla

Cell Reports, cilt.43, sa.1, 2024 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 43 Sayı: 1
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1016/j.celrep.2023.113630
  • Dergi Adı: Cell Reports
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE, Directory of Open Access Journals
  • Anahtar Kelimeler: AgRP, CP: Metabolism, CP: Neuroscience, diet-preference, endorphin, feeding, MOR, opioid, satiety
  • Dokuz Eylül Üniversitesi Adresli: Hayır

Özet

Opioids are generally known to promote hedonic food consumption. Although much of the existing evidence is primarily based on studies of the mesolimbic pathway, endogenous opioids and their receptors are widely expressed in hypothalamic appetite circuits as well; however, their role in homeostatic feeding remains unclear. Using a fluorescent opioid sensor, deltaLight, here we report that mediobasal hypothalamic opioid levels increase by feeding, which directly and indirectly inhibits agouti-related protein (AgRP)-expressing neurons through the μ-opioid receptor (MOR). AgRP-specific MOR expression increases by energy surfeit and contributes to opioid-induced suppression of appetite. Conversely, its antagonists diminish suppression of AgRP neuron activity by food and satiety hormones. Mice with AgRP neuron-specific ablation of MOR expression have increased fat preference without increased motivation. These results suggest that post-ingestion release of endogenous opioids contributes to AgRP neuron inhibition to shape food choice through MOR signaling.