{
  "abstract": "Semaglutide-induced weight loss requires neurons in the dorsal vagal complex (DVC), but how DVC-derived downstream brain circuits coordinate the drug's effects on feeding and metabolism is unknown. We show that semaglutide suppresses fasting-induced AgRP neuron activation through DVC neurons, including Adcyap1+ neurons of the nucleus of the solitary tract (Adcyap1NTS). Projection-specific optogenetic stimulation reveals that Adcyap1NTS inputs to the arcuate nucleus and dorsomedial hypothalamus non-aversively suppress feeding during elevated motivational drive, while sparing active-phase chow intake. Adcyap1NTS[->]arcuate stimulation additionally promotes food intake-independent ketogenesis and weight loss, while stimulation of the Adcyap1NTS[->]DMH pathway lowers energy expenditure. Crucially, stimulation of semaglutide-responsive NTS projections to both hypothalamic regions recapitulates key effects of the corresponding Adcyap1NTS pathways on palatable-food intake and metabolism, while also suppressing fasting-induced AgRP neuron activation, demonstrating that these pathway-specific functions are retained within neuronal circuits recruited by semaglutide. Together, our findings identify brainstem-to-hypothalamus circuit substrates through which semaglutide regulates motivated feeding and metabolic state downstream of the DVC.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Neuroscience and Physiology, University of Gothenburg"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "S. Blid Sköldheden"
    },
    {
      "name": "J. Teixidor-Deulofeu"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Ruud"
    },
    {
      "affs": [
        0
      ],
      "name": "L. Engström Ruud"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1gjmg6ctrv3fs.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.04.749561",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.04.749561v1.full",
  "id": "1gjmg6ctrv3fs",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.04.749561v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2807|Regulation of Appetite and Obesity"
    ]
  ],
  "openalex": "W7212078178",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.04.749561v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1gjmg6ctrv3fs.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:25Z",
      "native_id": "10.64898/2026.09.04.749561",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.04.749561v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Semaglutide engages distinct brainstem-to-hypothalamus circuits to suppress motivated feeding and regulate ketogenesis and energy expenditure",
  "title_text": "Semaglutide engages distinct brainstem-to-hypothalamus circuits to suppress motivated feeding and regulate ketogenesis and energy expenditure",
  "type": "preprint",
  "updated_at": "2026-10-30T12:20:25Z",
  "url": "https://research.draconitic.com/paper/1gjmg6ctrv3fs",
  "venue": "bioRxiv",
  "versions": []
}