{
  "abstract": "Background/Objectives: High-fat diet (HFD) feeding disrupts systemic metabolism and hypothalamic mechanisms that coordinate energy balance. Whether quercetin modifies coordinated hypothalamic transcription linking m6A-related regulation with leptin–insulin- and melanocortin-associated biology remains unclear. We examined the metabolic and hypothalamic transcriptional response to quercetin during chronic HFD exposure. Methods: Male Wistar rats were studied for 16 weeks in a 2 × 2 factorial design: Control (n = 8), Control + quercetin (n = 5), HFD (n = 5), and HFD + quercetin (n = 6). Quercetin was administered orally at 100 mg/kg/day. Body weight, fasting glucose, food/fluid intake, calculated energy intake, oral glucose tolerance, terminal adiposity, lipids, and a 21-transcript hypothalamic RT-qPCR panel were evaluated. Analyses included factorial models with HC3 inference and FDR control, PCA/PERMANOVA, predefined transcriptional modules, bootstrap and leave-one-sample-out sensitivity analyses, treatment-adjusted covariance, and shrinkage regularization. Results: At week 16, HFD + quercetin reduced glucose AUC relative to HFD by 2415 mg·min/dL (q = 0.0029), visceral fat by 5.16 g (q = 0.004), and triglycerides by 47.03 mg/dL (q < 0.001), without a corresponding difference in final body weight. Diet × quercetin interactions were supported for week-16 AUC, visceral adiposity, triglycerides, and 15 of 21 hypothalamic transcripts. Sixteen of 21 transcripts met robustness criteria for the HFD + quercetin versus HFD contrast. PC1 and PC2 captured 73.5% of transcriptional variance, and all three predefined transcriptional modules showed robust diet-dependent responses. Regularized covariance sensitivity preserved the direction of all 210 treatment-adjusted transcript associations. Conclusions: The principal metabolic effects of quercetin were predominantly evident under HFD conditions and were accompanied by coordinated hypothalamic transcriptional remodeling across m6A-related, leptin–insulin-associated, and melanocortin-associated domains. These data define a transcriptional architecture for mechanistic follow-up without implying direct measurement of circulating leptin or insulin, m6A activity, protein abundance, or pathway activation.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratorio de Biología Molecular, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico",
    "Laboratorio de Farmacología y Medicina Hiperbárica Experimental, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Alexis Alejandro García-Rivero"
    },
    {
      "affs": [
        0
      ],
      "name": "Ángel Miliar-García",
      "orcid": "0000-0003-3958-0869"
    },
    {
      "affs": [
        0
      ],
      "name": "Antonio Ávila-Guerrero",
      "orcid": "0009-0002-0822-3455"
    },
    {
      "affs": [
        0
      ],
      "name": "María de los Ángeles Martínez-Godínez"
    },
    {
      "affs": [
        1
      ],
      "name": "María del Carmen Castillo-Hernández",
      "orcid": "0000-0003-1192-6776"
    },
    {
      "affs": [
        1
      ],
      "name": "Gustavo Guevara-Balcázar"
    },
    {
      "affs": [
        0
      ],
      "name": "Aarón Domínguez-López"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fq2m2a7f1wtka.bib",
  "cited_by": 0,
  "doi": "10.3390/metabo16100773",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13706927/?tool=EBI",
  "id": "fq2m2a7f1wtka",
  "issns": [
    "2218-1989"
  ],
  "landing_url": "https://www.mdpi.com/2218-1989/16/10/773",
  "language": "eng",
  "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": [
    [
      "openalex",
      "2807|Regulation of Appetite and Obesity"
    ]
  ],
  "openalex": "W7213458628",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13706927/pdf/?tool=EBI",
  "pmcid": "PMC13706927",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/fq2m2a7f1wtka.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:00Z",
      "native_id": "10.3390/metabo16100773",
      "source": "crossref",
      "url": "https://www.mdpi.com/2218-1989/16/10/773"
    },
    {
      "first_seen": "2026-10-30T12:21:49Z",
      "native_id": "PMC:PMC13706927",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13706927"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2807|Regulation of Appetite and Obesity",
      "subfield": "physiology"
    }
  ],
  "title": "Quercetin Attenuates Metabolic Dysfunction and Reshapes Hypothalamic m6A-Related, Leptin–Insulin, and Melanocortin-Associated Transcription in High-Fat-Diet-Fed Rats",
  "title_text": "Quercetin Attenuates Metabolic Dysfunction and Reshapes Hypothalamic m6A-Related, Leptin–Insulin, and Melanocortin-Associated Transcription in High-Fat-Diet-Fed Rats",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:49Z",
  "url": "https://research.draconitic.com/paper/fq2m2a7f1wtka",
  "venue": "Metabolites",
  "versions": []
}