Thomas 2012: TOFI - Thin Outside Fat Inside

Background

Dr. E. Louise Thomas and colleagues from Imperial College London published this study in Obesity (PMID: 21660078), describing the TOFI (Thin Outside, Fat Inside) phenotype using MRI and MRS imaging.

Study Design

Design: Cross-sectional imaging study Population: Adults stratified by BMI category Imaging: Whole-body MRI for fat distribution, MRS for organ fat content Focus: Identifying metabolically unhealthy normal-weight individuals

Key Findings

TOFI characteristics:

Feature	TOFI Individuals	Healthy Lean
BMI	Normal (<25)	Normal (<25)
Visceral fat	Elevated	Low
Liver fat	Elevated	Low
Subcutaneous fat	Low	Low
Metabolic profile	Abnormal	Normal

Prevalence: Approximately 10-15% of normal-BMI individuals had TOFI phenotype.

Best predictor of TOFI: Waist circumference (not BMI)

Mechanistic Insights

TOFI individuals have:

1. •Preferential fat storage in visceral depot
2. •Limited subcutaneous fat expansion capacity ("adipose tissue overflow")
3. •Ectopic fat deposition in liver and muscle
4. •Insulin resistance despite normal weight

May reflect genetic predisposition or prenatal programming.

Clinical Implications

Normal BMI does not guarantee metabolic health. Screening should include:

• •Waist circumference
• •Waist-to-height ratio (WHtR)
• •Metabolic markers (TG, HDL, glucose, ALT)

Metabolic Health Perspective

TOFI validates the metabolic optimization approach: focus on metabolic markers, not weight. The "invisible" fat around organs drives metabolic disease. WHtR >0.5 identifies at-risk individuals regardless of BMI.