{
  "abstract": "Obesity is a major risk factor for insulin resistance and type 2 diabetes. Adipocyte stress responses can either promote metabolic dysfunction or preserve insulin action, but the contribution of the p38 MAPK activator MKK3 to adipose tissue physiology remains poorly understood. Here, we show that adipose MKK3 expression increases early during high-fat feeding and is also elevated in human obesity. In human visceral adipose tissue, MKK3 expression was positively associated with body mass index and leptin and inversely associated with HbA1c in unadjusted analyses. Using germline, Fabp4-Cre, and Adipo-Cre Mkk3-deficient mice, together with p38β-deficient mice and primary adipocytes, we found that loss of adipocyte MKK3 impairs insulin responsiveness. Adipo-Cre;Mkk3fl/fl (AdipoMkk3) mice displayed reduced insulin-stimulated glucose uptake selectively in subcutaneous white adipose tissue despite unchanged body composition and basal brown adipose tissue activity. Mechanistically, MKK3 or p38β deficiency increased p70S6K activity and inhibitory IRS1 Ser307 phosphorylation, reduced GLUT4 translocation and Akt activation, and these defects were partially rescued by rapamycin or the selective p70S6K inhibitor PF-4708671. Together, these findings identify an adipocyte MKK3-p38β-p70S6K axis that helps preserve insulin signaling during nutritional stress.",
  "abstract_shown": true,
  "affiliations": [
    "Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.",
    "Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.",
    "Complejo Asistencial de Zamora, Zamora, Spain.",
    "Bariatric Surgery Unit, Department of General Surgery, University Hospital of Salamanca, Department of Surgery, University of Salamanca, Salamanca, Spain.",
    "Department of Physiology, CiMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.",
    "Division of Cell Signalling and Immunology, Faculty of Life Sciences, University of Dundee, Dundee, UK.",
    "Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.",
    "Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.",
    "Program in Molecular Medicine, University of Massachusetts Chan Medical School, Massachusetts, USA.",
    "Department of Internal Medicine, University Hospital of Salamanca-IBSAL, Salamanca, Spain.",
    "Department of Medicine, University of Salamanca, Salamanca, Spain."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Edgar Bernardo",
      "orcid": "0000-0002-0500-9632"
    },
    {
      "affs": [
        1
      ],
      "name": "Nuria Matesanz"
    },
    {
      "affs": [
        2
      ],
      "name": "Jorge-Luis Torres"
    },
    {
      "affs": [
        0
      ],
      "name": "Alba C Arcones",
      "orcid": "0000-0001-8182-4973"
    },
    {
      "affs": [
        0
      ],
      "name": "Juan Ignacio Jiménez-Loygorri",
      "orcid": "0000-0002-3065-9952"
    },
    {
      "affs": [
        0
      ],
      "name": "Alfonso Mora",
      "orcid": "0000-0002-6397-4836"
    },
    {
      "affs": [
        1
      ],
      "name": "Leticia Herrera-Melle"
    },
    {
      "affs": [
        0
      ],
      "name": "Luis Leiva-Vega",
      "orcid": "0000-0002-0050-8117"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Elena Rodriguez"
    },
    {
      "affs": [
        3
      ],
      "name": "Lourdes Hernández-Cosido",
      "orcid": "0000-0003-1359-7478"
    },
    {
      "affs": [
        0
      ],
      "name": "Marta Leon",
      "orcid": "0009-0005-4170-341X"
    },
    {
      "affs": [
        0
      ],
      "name": "Paula Yong González"
    },
    {
      "affs": [
        0
      ],
      "name": "Teresa Durán",
      "orcid": "0009-0006-7153-4343"
    },
    {
      "affs": [
        4
      ],
      "name": "Tamara Parracho",
      "orcid": "0000-0001-9283-4464"
    },
    {
      "affs": [
        0
      ],
      "name": "Francisca Mulero",
      "orcid": "0000-0001-9584-4211"
    },
    {
      "affs": [
        4
      ],
      "name": "Rubén Nogueiras",
      "orcid": "0000-0002-9976-9930"
    },
    {
      "affs": [
        5
      ],
      "name": "J Simon C Arthur",
      "orcid": "0000-0002-8135-1958"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Angel R Nebreda",
      "orcid": "0000-0002-7631-4060"
    },
    {
      "affs": [
        8
      ],
      "name": "Roger J Davis",
      "orcid": "0000-0002-0130-1652"
    },
    {
      "affs": [
        9,
        10
      ],
      "name": "Miguel Marcos",
      "orcid": "0000-0003-1269-4487"
    },
    {
      "affs": [
        0
      ],
      "name": "Guadalupe Sabio",
      "orcid": "0000-0002-2822-0625"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/72baq831xecvs.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.202520388",
  "fulltext_url": "https://europepmc.org/articles/PMC13717117",
  "id": "72baq831xecvs",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://europepmc.org/article/MED/42952173",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2713|Adipokines, Inflammation, and Metabolic Diseases"
    ]
  ],
  "openalex": "W7224581719",
  "pdf_url": "https://europepmc.org/articles/PMC13717117?pdf=render",
  "pmcid": "PMC13717117",
  "pmid": "42952173",
  "published": "2026-10-28",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/72baq831xecvs.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:33Z",
      "native_id": "MED:42952173",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42952173"
    },
    {
      "first_seen": "2026-11-02T12:21:30Z",
      "native_id": "PMC13717117",
      "source": "pmc",
      "url": "https://doi.org/10.1002/advs.202520388"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Adipokines, Inflammation, and Metabolic Diseases",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "An Adipocyte MKK3-p38β Axis Preserves Insulin Responsiveness in Mice and Is Reciprocally Altered in Human Obesity.",
  "title_text": "An Adipocyte MKK3-p38β Axis Preserves Insulin Responsiveness in Mice and Is Reciprocally Altered in Human Obesity.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:21:30Z",
  "url": "https://research.draconitic.com/paper/72baq831xecvs",
  "venue": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)",
  "versions": []
}