Abstract
ObjectivesTo determine if caloric restriction (CR) would cause changes in plasma metabolic intermediates in response to a mixed meal, suggestive of changes in the capacity to adapt fuel oxidation to fuel availability or metabolic flexibility, and to determine how any such changes relate to insulin sensitivity (SI).MethodsForty-six volunteers were randomized to a weight maintenance diet (Control), 25% CR, or 12.5% CR plus 12.5% energy deficit from structured aerobic exercise (CR+EX), or a liquid calorie diet (890 kcal/d until 15% reduction in body weight)for six months. Fasting and postprandial plasma samples were obtained at baseline, three, and six months. A targeted mass spectrometry-based platform was used to measure concentrations of individual free fatty acids (FFA), amino acids (AA), and acylcarnitines (AC). SI was measured with an intravenous glucose tolerance test.ResultsOver three and six months, there were significantly larger differences in fasting-to-postprandial (FPP) concentrations of medium and long chain AC (byproducts of FA oxidation) in the CR relative to Control and a tendency for the same in CR+EX (CR-3 month P = 0.02; CR-6 month P = 0.002; CR+EX-3 month P = 0.09; CR+EX-6 month P = 0.08). After three months of CR, there was a trend towards a larger difference in FPP FFA concentrations (P = 0.07; CR-3 month P = 0.08). Time-varying differences in FPP concentrations of AC and AA were independently related to time-varying SI (P<0.05 for both).ConclusionsBased on changes in intermediates of FA oxidation following a food challenge, CR imparted improvements in metabolic flexibility that correlated with improvements in SI.Trial RegistrationClinicalTrials.gov NCT00099151
Highlights
Caloric restriction provides metabolic benefits in a variety of nonhuman animal species
While the primary aim of the original study was to determine the impact of caloric restriction on biomarkers of longevity and metabolic adaptation, the secondary aims of CALERIE were to evaluate the impact of caloric restriction on risk factors for type 2 diabetes mellitus and cardiovascular disease
After a balanced mixed meal, glucose is oxidized in the brain and other organs while lipolysis in adipose tissue and glycogenolysis in the liver are inhibited by increases in insulin levels induced by the ingested calories
Summary
Caloric restriction provides metabolic benefits in a variety of nonhuman animal species (reviewed in [1]). While the primary aim of the original study was to determine the impact of caloric restriction on biomarkers of longevity and metabolic adaptation, the secondary aims of CALERIE were to evaluate the impact of caloric restriction on risk factors for type 2 diabetes mellitus and cardiovascular disease. Efficient substrate switching after a mixed meal manifests as a decrease in fatty acid oxidation and a fall in circulating free fatty acids and intermediates of fatty acid oxidation [2,3] Impairment in this normal mode of substrate switching is associated with obesity, skeletal muscle insulin resistance, metabolic syndrome, and type 2 diabetes mellitus [3,4,5]
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