{
  "abstract": "Obesity and anxiety disorders are frequently comorbid, yet the neural circuit mechanisms linking metabolic and affective states remain incompletely understood. Here, in male mice exposed to long-term high-fat diet, we identify a hypothalamic circuit comprising arcuate nucleus agouti-related protein neurons and paraventricular nucleus corticotropin-releasing hormone neurons that regulates anxiety-like behavior under metabolic stress, with downstream recruitment of lateral hypothalamic area glutamatergic neurons to modulate feeding in a state-dependent manner. In vivo fiber photometry and ex vivo electrophysiology show that high-fat diet enhances activity and feeding-locked recruitment of this circuit, associated with increased anxiety-like behavior and feeding. Circuit-specific inhibition attenuates both phenotypes, whereas corticotropin-releasing hormone receptor 2 signaling in the lateral hypothalamic area selectively mediates high-fat diet-associated hyperphagia without affecting anxiety-like behavior. In this work, we show a disease-state-dependent hypothalamic circuit differentially recruited under chronic high-fat diet to coordinate anxiety-related behavior and feeding output, providing a framework for metabolic-affective interactions.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Anaesthesiology, the First Affiliated Hospital of Anhui Medical University, Key Laboratory of Anaesthesia and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, China.",
    "School of Nursing, Anhui Medical University, Hefei, China.",
    "Department of Anaesthesiology, the First Affiliated Hospital of Anhui Medical University, Key Laboratory of Anaesthesia and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, China. gaolinqiu@fy.ahmu.edu.cn.",
    "Department of Anaesthesiology, the First Affiliated Hospital of Anhui Medical University, Key Laboratory of Anaesthesia and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, China. yfy1023275@fy.ahmu.edu.cn.",
    "Department of Anaesthesiology, the First Affiliated Hospital of Anhui Medical University, Key Laboratory of Anaesthesia and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, China. liuxuesheng@ahmu.edu.cn.",
    "School of Nursing, Anhui Medical University, Hefei, China. liuxuesheng@ahmu.edu.cn."
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Peng Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jun Li"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xin Cheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Wei Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhengyu Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Zheng Fang"
    },
    {
      "affs": [
        0
      ],
      "name": "Dijia Wang",
      "orcid": "0000-0003-4808-7451"
    },
    {
      "affs": [
        0
      ],
      "name": "Bin Mei"
    },
    {
      "affs": [
        0
      ],
      "name": "Hu Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Shaohua Hu"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhilai Yang",
      "orcid": "0009-0003-0597-4269"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiqian Zhang",
      "orcid": "0000-0001-6360-1557"
    },
    {
      "affs": [
        2
      ],
      "name": "Gaolin Qiu"
    },
    {
      "affs": [
        3
      ],
      "name": "Xin Qing"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Xuesheng Liu",
      "orcid": "0000-0003-3779-2964"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/byrrzwm0f5fk4.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-77749-w",
  "fulltext_url": "https://europepmc.org/articles/PMC13677739",
  "id": "byrrzwm0f5fk4",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://europepmc.org/article/MED/42893998",
  "language": "eng",
  "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": [
    [
      "openalex",
      "2807|Regulation of Appetite and Obesity"
    ]
  ],
  "openalex": "W7213240495",
  "pdf_url": "https://europepmc.org/articles/PMC13677739?pdf=render",
  "pmcid": "PMC13677739",
  "pmid": "42893998",
  "published": "2026-09-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/byrrzwm0f5fk4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:41Z",
      "native_id": "MED:42893998",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42893998"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2807|Regulation of Appetite and Obesity",
      "subfield": "physiology"
    }
  ],
  "title": "A hypothalamic circuit links high-fat diet exposure to anxiety-like behavior and anxiety-associated hyperphagia.",
  "title_text": "A hypothalamic circuit links high-fat diet exposure to anxiety-like behavior and anxiety-associated hyperphagia.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:41Z",
  "url": "https://research.draconitic.com/paper/byrrzwm0f5fk4",
  "venue": "Nature communications",
  "versions": []
}