Association Between Fasting Substrate Utilization and Adipose Tissue Distribution

Background and Aim: Metabolic flexibility is crucial for health. While reduced fatty acid utilization often correlates with obesity, its relationship with specific fat depots in nonobese individuals remains unclear. This study investigated the association between fasting substrate utilization, measured via respiratory exchange ratio (RER), and abdominal fat distribution (visceral and subcutaneous) across BMI categories. Methods and Results: In a retrospective study of 15,022 participants, fasting RER was measured via indirect calorimetry. Participants were categorized by metabolic phenotype: Predominant Fat Oxidation (RER < 0.775) or Predominant Glucose Oxidation (RER > 0.925). Visceral (VAT) and subcutaneous adipose tissue (SAT) were assessed via ultrasound, adjusting for age, sex, and menopause. In underweight/normal weight individuals, predominant glucose oxidation correlated with significantly higher VAT (adjusted difference = 0.40 cm; p < 0.001) and lower SAT (adjusted difference = -0.16 cm; p = 0.039) compared to predominant fat oxidation. A similar trend persisted in overweight participants but was attenuated in obesity, where predominant glucose oxidation was associated with lower overall body fat. Conclusions: Higher fasting RER, indicating predominant glucose oxidation, was associated with adverse fat distribution (higher visceral, lower subcutaneous fat) in this cohort, particularly in normal-BMI individuals. Fasting RER warrants further investigation as a potential non-invasive indicator of metabolic risk and ectopic fat deposition prior to obesity development.