Metabolic Vulnerability Despite Normal BMI: From Adverse Body Composition to Ectopic Fat and Organ Dysfunction.

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Abstract

BMI remains the most widely used measure for defining overweight and obesity; however, it does not adequately capture body fat distribution, skeletal muscle mass and quality, adipose tissue function, or ectopic fat accumulation. Consequently, individuals with a normal BMI may exhibit substantial metabolic abnormalities, whereas some individuals with obesity remain relatively metabolically healthy. These observations challenge the assumption that BMI reliably reflects metabolic health and highlight the concept of metabolic vulnerability despite normal body weight. This narrative review examines the biological basis of this metabolic vulnerability and evaluates the evidence supporting a shift from BMI-centered assessment toward body composition-based phenotyping. We discuss the interrelated roles of impaired adipose tissue expandability and function, visceral adiposity, chronic low-grade inflammation, adipose tissue fibrosis, skeletal muscle dysfunction, and ectopic lipid deposition in the development of insulin resistance and organ-specific metabolic dysfunction. Particular emphasis is placed on adipose tissue dysfunction as a potential unifying mechanism underlying metabolic heterogeneity among individuals with similar BMI. The review further examines adverse body composition across normal-weight metabolic phenotypes, including normal-weight obesity (NWO), metabolically unhealthy normal weight (MUNW), lean prediabetes, lean T2DM, lean MASLD, hypertension, cardiovascular disease, and chronic kidney disease. Excess visceral adiposity, unfavorable fat-to-lean mass distribution, impaired skeletal muscle quality, and ectopic fat accumulation in the liver, pancreas, heart, skeletal muscle, and other organs may contribute to metabolic risk independently of BMI. We also summarize advances in body composition and ectopic fat assessment, including dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging (MRI), computed tomography (CT), bioelectrical impedance analysis (BIA), and artificial intelligence-assisted imaging, together with emerging therapeutic strategies focused on reducing visceral and ectopic fat, preserving skeletal muscle, and restoring metabolic tissue function rather than pursuing weight loss alone. Moving beyond BMI toward integrated assessment of body composition, adipose tissue biology, and ectopic fat distribution may improve recognition of metabolic vulnerability, facilitate earlier identification of individuals at increased cardiometabolic risk, and support more precise prevention and treatment strategies.

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