Effect of Caloric Restriction with and without Exercise on Metabolic Intermediates in Nonobese Men and Women

Greater improvement in insulin sensitivity with weight loss during calorie restriction and exercise interventions may be related to improved coupling of β-oxidation and tricarboxylic acid cycle flux. Objectives: The objective of the study was to evaluate whether serum concentrations of metabolic intermediates are related to adiposity and insulin sensitivity (Si) in overweight healthy subjects and compare changes in metabolic intermediates with similar weight loss achieved by diet only or diet plus exercise. Design: This was a randomized controlled trial. Participants and Intervention: The cross-sectional study included 46 (aged 36.8 ± 1.0 yr) overweight (body mass index 27.8 ± 0.7 kg/m2) subjects enrolled in a 6-month study of calorie restriction. To determine the effect of diet only or diet plus exercise on metabolic intermediates, 35 subjects were randomized to control (energy intake at 100% of energy requirements); CR (25% calorie restriction), or CR+EX: (12.5% CR plus 12.5% increase in energy expenditure by exercise). Main Outcome Measures: Serum concentrations of eight fatty acids, 15 amino acids, and 45 acylcarnitines (ACs) measured by targeted mass spectrometry. Results: In overweight subjects, the concentrations of C2 AC and long-chain ACs were positively associated with percent fat (R2 = 0.75, P = 0.0001) and Si (R2 = 0.12, P = 0.05). The percent fat (R2 = 0.77, P < 0.0001), abdominal visceral fat (R2 = 0.64, P < 0.0001), and intrahepatic fat (R2 = 0.30, P = 0.0002) were positively associated with fatty acid concentrations. There was a significant increase in an AC factor (comprised of C2 and several medium chain ACs) in the CR group (P = 0.01). Conclusion: In nonobese subjects, fasted serum ACs are associated with Si and fat mass. Despite similar weight loss, serum ACs increase with CR alone but not CR+EX. A greater improvement in Si with weight loss during CR+EX interventions may be related to improved coupling of β-oxidation and tricarboxylic acid cycle flux induced by exercise.