{
  "abstract": "Body mass index (BMI) is widely used in clinical practice, but it does not directly reflect fat distribution, ectopic adiposity, or adipose tissue function. Individuals with a normal or near-normal BMI may still have excess visceral fat. The Thin Outside, Fat Inside (TOFI) phenotype describes this mismatch between external body size and internal adiposity. This structured narrative review examined TOFI and related normal-weight phenotypes, focusing on visceral and ectopic fat, adipose tissue dysfunction, molecular mechanisms, imaging, and organ-specific risk. A literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science for English-language studies published mainly between 2021 and 2026. Earlier seminal and directly relevant studies were also included. Evidence from related human phenotypes and experimental models suggests that impaired adipose tissue expandability, visceral and ectopic fat accumulation, inflammation, mitochondrial stress, and lipotoxicity may help explain metabolic dysfunction despite a normal BMI. These mechanisms remain incompletely characterized in populations explicitly defined as TOFI. Preclinical models and imaging methods may help characterize TOFI-like features. Diagnostic criteria are still heterogeneous, and TOFI-specific longitudinal and intervention data remain limited. TOFI may serve as a useful translational framework for identifying hidden adiposity and metabolic risk in individuals with a normal BMI.",
  "abstract_shown": true,
  "affiliations": [
    "Principles and Practice of Clinical Research Program, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA",
    "Department of Anatomy, Faculty of General Medicine, Ovidius University, 900470 Constanța, Romania",
    "Centre for Diabetes Care, Greater Noida 201310, India",
    "Department of Medicine, Kasturba Medical College, Manipal Academy of Higher Education (MAHE), Manipal 576104, India",
    "Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, DC 20052, USA",
    "Grupo de Investigación Neurociencias, Metabolismo, Efectividad Clínica y Sanitaria (NEMECS), Universidad Científica del Sur, Lima 15001, Peru",
    "RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates",
    "Vascular Surgery Department, Hospital de Clínicas Dr. Manuel Quintela, Montevideo 11600, Uruguay",
    "City University of São Paulo (UNICID), São Paulo 05305-000, Brazil",
    "WHO Collaborating Centre, Imperial College London, London SW7 2AZBW, UK",
    "Department of Health and Kinesiology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA",
    "Universidad Peruana Unión, Lima 15472, Peru",
    "RAK College of Medical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates",
    "School of Medicine, PROMISE Department of Health Promotion Sciences, Maternal and Infantile Care, Internal Medicine and Medical Specialties, University of Palermo, 90133 Palermo, Italy"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Sorina Ispas",
      "orcid": "0009-0000-3401-1232"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Amit Gupta",
      "orcid": "0000-0002-1221-2217"
    },
    {
      "affs": [
        4
      ],
      "name": "Maria Diaz-Gutierrez",
      "orcid": "0000-0001-5029-8026"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Victor Velásquez-Rimachi"
    },
    {
      "affs": [
        0
      ],
      "name": "Zamar Anyela Malca Calderon",
      "orcid": "0000-0002-1384-9797"
    },
    {
      "affs": [
        6
      ],
      "name": "Syed Arman Rabbani",
      "orcid": "0000-0002-8454-8158"
    },
    {
      "affs": [
        7
      ],
      "name": "Dario Madera"
    },
    {
      "affs": [
        8
      ],
      "name": "Ana Clara Felix de Farias Santos",
      "orcid": "0009-0004-0007-0866"
    },
    {
      "affs": [
        9
      ],
      "name": "Sunil Kumar",
      "orcid": "0009-0006-8322-0114"
    },
    {
      "affs": [
        0,
        10
      ],
      "name": "Jerry Li",
      "orcid": "0009-0001-3942-6549"
    },
    {
      "affs": [
        0,
        11
      ],
      "name": "Darlene Hannele Huanca Salazar",
      "orcid": "0009-0004-7738-9621"
    },
    {
      "affs": [
        1
      ],
      "name": "Viorel Ispas"
    },
    {
      "affs": [
        12
      ],
      "name": "Imran Rashid Rangraze"
    },
    {
      "affs": [
        6,
        13
      ],
      "name": "Manfredi Rizzo",
      "orcid": "0000-0002-9549-8504"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/632e5dwrs5hcq.bib",
  "cited_by": 0,
  "doi": "10.3390/biom16111543",
  "fulltext_url": null,
  "id": "632e5dwrs5hcq",
  "issns": [
    "2218-273X"
  ],
  "landing_url": "https://www.mdpi.com/2218-273X/16/11/1543",
  "language": null,
  "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",
      "2705|Cardiovascular Disease and Adiposity"
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  "openalex": "W7223199879",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-22",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/632e5dwrs5hcq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:59Z",
      "native_id": "10.3390/biom16111543",
      "source": "crossref",
      "url": "https://www.mdpi.com/2218-273X/16/11/1543"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2705|Cardiovascular Disease and Adiposity",
      "subfield": "cardiovascular"
    }
  ],
  "title": "Beyond BMI: Mapping Clinical, Mechanistic, and Imaging Evidence Relevant to the Thin Outside, Fat Inside Phenotype",
  "title_text": "Beyond BMI: Mapping Clinical, Mechanistic, and Imaging Evidence Relevant to the Thin Outside, Fat Inside Phenotype",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:59Z",
  "url": "https://research.draconitic.com/paper/632e5dwrs5hcq",
  "venue": "Biomolecules",
  "versions": []
}