{
  "abstract": "Temperature is a fundamental determinant of mammalian metabolism. The canonical cold-adaptation pathway involves cold sensing by peripheral sensory neurons, which activate sympathetic outflow, {beta}-adrenergic signaling, and lipolysis in adipose tissue. In contrast, we report here a cell-intrinsic mechanism by which physiologically relevant cooling temperatures (27-31 oC) enhance lipolysis in subcutaneous adipose tissue. Mechanistically, cooling drives liquid-liquid phase separation (LLPS) of perilipin 1 (PLIN1), the dominant lipid droplet coat protein, promoting its condensation and the local recruitment of PKA to the droplet surface. This spatial reorganization selectively amplified PKA-mediated perilipin 1 phosphorylation, CGI-58 release, and ATGL-dependent lipolysis. The process depends on the intrinsically disordered region (IDR) of perilipin1, where four aromatic residues, conserved in endotherms but not in ectotherms, are required for cooling-induced LLPS and lipolysis in vivo. Notably, targeted delivery of an LLPS-competent perilipin 1 variant to the inguinal adipose tissue of mice enhanced local lipolysis and reduced depot mass. Together, these findings uncover a cell-intrinsic thermosensitive mechanism that can tune lipolytic responsiveness, offering a possible strategy for targeted depot-selective fat reduction.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA",
    "Howard Hughes Medical Institute, Chevy Chase, VA, USA",
    "Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA",
    "Harvard/MIT MD-PhD Program, Biological and Biomedical Sciences Program, Boston, MA, USA; Harvard/MIT Program in Health, Sciences, and Technology, Cambridge, MA, USA"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yong Chen",
      "orcid": "0000-0002-0723-8105"
    },
    {
      "affs": [
        2
      ],
      "name": "Li Chen"
    },
    {
      "affs": [
        0,
        1,
        3
      ],
      "name": "Zezhou Zhao"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Tian Lu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Youchen Guan"
    },
    {
      "affs": [
        0
      ],
      "name": "Zinger Yang Loureiro"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Shingo Kajimura",
      "orcid": "0000-0003-0672-5910"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8j312ma8mwspp.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.22.760470",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.760470v1.full",
  "id": "8j312ma8mwspp",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.760470v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2737|Adipose Tissue and Metabolism"
    ]
  ],
  "openalex": "W7223905111",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.760470v1.full.pdf",
  "pmcid": "PMC13733734",
  "pmid": "42990164",
  "published": "2026-10-22",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/8j312ma8mwspp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:53Z",
      "native_id": "10.64898/2026.10.22.760470",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.22.760470v1"
    },
    {
      "first_seen": "2026-11-08T12:23:26Z",
      "native_id": "PMC13733734",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.22.760470"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "A Cell-Autonomous Cold Sensor Promotes Lipolysis Through Phase Separation",
  "title_text": "A Cell-Autonomous Cold Sensor Promotes Lipolysis Through Phase Separation",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:26Z",
  "url": "https://research.draconitic.com/paper/8j312ma8mwspp",
  "venue": "bioRxiv",
  "versions": []
}