Key result
TOFI phenotype links impaired fat expandability and ectopic lipid storage to heightened cardiometabolic risk despite normal BMI.
Why the study?
Body mass index does not directly reflect fat distribution, ectopic adiposity, or adipose tissue function, and individuals with a normal or near-normal BMI may still harbor excess visceral fat, known as the Thin Outside, Fat Inside (TOFI) phenotype.
The Thin Outside, Fat Inside (TOFI) phenotype serves as a useful translational framework for identifying hidden visceral/ectopic adiposity and metabolic risk in individuals with a normal BMI, grounded in mechanisms like impaired adipose tissue expandability, inflammation, mitochondrial stress, and lipotoxicity.
Supports TOFI recognition for hidden cardiometabolic risk beyond BMI; leaves open standardized diagnostics and prospective trials.
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.
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Ispas et al. (2026) conducted a review in Thin Outside, Fat Inside (TOFI) phenotype and related normal-weight adiposity phenotypes. Thin Outside, Fat Inside (TOFI) phenotype (excess visceral and ectopic adiposity with normal BMI) vs. Normal-weight non-obese individuals without excess internal or visceral adiposity was evaluated. The Thin Outside, Fat Inside (TOFI) phenotype links impaired subcutaneous fat expandability and visceral/ectopic lipid deposition to insulin resistance and cardiometabolic risk despite a normal BMI.
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