{
  "abstract": "Background: The liver–adipose axis regulates insulin sensitivity and lipid metabolism, and its dysregulation contributes to metabolic disorders. PE/2, a semisynthetic derivative of the marine natural product phosphoeleganin, reduces IL-6 expression and secretion, enhancing insulin sensitivity in liver cells (HepG2). However, its role in liver–adipose communication is unclear.\n\nMethods: To clarify the impact of PE/2 on liver–adipose tissue crosstalk, the conditioned media approach was used. Protein and mRNA levels were analyzed by Western blot and Real-Time RT-PCR, respectively. Lipid and glucose metabolism were evaluated by Oil Red O staining and glucose consumption assays, respectively.\n\nResults: Our results indicate that in 3T3-L1 adipocytes, conditioned media derived from PE/2-treated HepG2 cells (CM PE/2 ) increased adiponectin expression by 1.85-fold and reduced interleukin-8 and interleukin-1β mRNA levels by 43% and 52%, respectively, compared with conditioned media alone (CM). The protective adipokine phenotype induced by CM PE/2 was accompanied by 1.75-fold lipid accumulation and increased expression of adipogenic markers, including PPARγ , C/EBPα , GLUT4 , and FABP4 . To examine whether this profile translates into enhanced insulin sensitivity, we evaluated the insulin pathway. Interestingly, CM from insulin-stimulated HepG2 cells (CM Ins ) did not significantly increase insulin receptor (INSR) or Akt phosphorylation compared with CM from 3T3-L1 adipocytes. However, CM derived from HepG2 co-treated with insulin and PE/2 (CM Ins+PE/2 ) increased INSR and Akt phosphorylation by 2.13- and 1.63-fold, respectively, compared to CM, and by 1.83- and 1.42-fold, respectively, compared to CM Ins . Consistently, 3T3-L1 glucose consumption significantly improved in the presence of CM Ins+PE/2 . Treatment with the PI3K/Akt inhibitor LY294002 reversed the effects of CM Ins+PE/2 . Finally, supplementing recombinant IL-6 into CM PE/2- treated cells reduced the effect of this compound on the expression of inflammatory and adipogenic genes and on glucose consumption in 3T3-L1 adipocytes, corroborating the hypothesis that IL-6 is involved in the action mediated by PE/2.\n\nConclusion: These findings suggest that PE/2 improves the metabolic–inflammatory profile in adipocytes by modulating hepatocyte–adipocyte crosstalk, highlighting its implication for metabolic dysfunctions associated with impaired liver-adipose communication.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Translational Medicine, University of Naples Federico II",
    "Department of Pharmacy, University of Naples Federico II"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
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        0
      ],
      "name": "Federica Mormone"
    },
    {
      "affs": [
        0
      ],
      "name": "Giusy Ferraro"
    },
    {
      "affs": [
        0
      ],
      "name": "Cristina Morelli"
    },
    {
      "affs": [
        0
      ],
      "name": "Francesca Fiory"
    },
    {
      "affs": [
        0
      ],
      "name": "Serena Cabaro"
    },
    {
      "affs": [
        0
      ],
      "name": "Giuseppe Perruolo"
    },
    {
      "affs": [
        1
      ],
      "name": "Marcello Casertano"
    },
    {
      "affs": [
        1
      ],
      "name": "Marialuisa Menna"
    },
    {
      "affs": [
        0
      ],
      "name": "Pietro Formisano"
    },
    {
      "affs": [
        1
      ],
      "name": "Concetta Imperatore"
    },
    {
      "affs": [
        0
      ],
      "name": "Francesco Oriente"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5twv5nxwnkaty.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1909848",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1909848/full",
  "id": "5twv5nxwnkaty",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1909848/full",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RM1-950"
    ],
    [
      "openalex",
      "2713|Adipokines, Inflammation, and Metabolic Diseases"
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  "openalex": "W7223358717",
  "pdf_url": "https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1909848/pdf",
  "pmcid": "PMC13739515",
  "pmid": "42996389",
  "published": "2026-10-23",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/5twv5nxwnkaty.ris",
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Adipokines, Inflammation, and Metabolic Diseases",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Conditioned media derived from HepG2 cells treated with phosphoeleganin synthetic-derived compound PE/2 improve cytokine balance and metabolic response in 3T3-L1 adipocytes",
  "title_text": "Conditioned media derived from HepG2 cells treated with phosphoeleganin synthetic-derived compound PE/2 improve cytokine balance and metabolic response in 3T3-L1 adipocytes",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T15:20:41Z",
  "url": "https://research.draconitic.com/paper/5twv5nxwnkaty",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}