Seven-day overfeeding enhances adipose tissue dietary fatty acid storage and decreases myocardial and skeletal muscle dietary fatty acid partitioning in healthy subjects.

Increased myocardial partitioning of dietary fatty acids (DFA) and decreased left ventricular (LV) function is associated with insulin resistance in prediabetes. We hypothesized that enhanced myocardial DFA partitioning and reduced LV function might be induced concomitantly with reduced insulin sensitivity upon a 7-day hypercaloric (+50% in caloric intake), high-saturated fat (~11%energy), and simple carbohydrates (~54%energy) diet (HIGHCAL) versus an isocaloric diet (ISOCAL) with a moderate amount of saturated fat (~8%energy) and carbohydrates (~50%energy). Thirteen healthy subjects (7 men/6 women) underwent HIGHCAL versus ISOCAL in a randomized crossover design, with organ-specific DFA partitioning and LV function measured using the oral 14()-[F]fluoro-6-thia-heptadecanoic acid and [C]acetate positron emission tomography methods at the end of both interventions.

Seven-Day Caloric and Saturated Fat Restriction Increases Myocardial Dietary Fatty Acid Partitioning in Impaired Glucose-Tolerant Subjects.

Subjects with impaired glucose tolerance (IGT) have increased myocardial partitioning of dietary fatty acids (DFAs) with left ventricular dysfunction, both of which are improved by modest weight loss over 1 year induced by lifestyle changes. Here, we determined the effects of a 7-day hypocaloric diet (-500 kcal/day) low in saturated fat (<7% of energy) (LOWCAL study) versus isocaloric with the usual amount saturated fat (∼10% of energy) diet (ISOCAL) on DFA metabolism in subjects with IGT. Organ-specific DFA partitioning and cardiac and hepatic DFA fractional uptake rates were measured in 15 IGT subjects (7 males/8 females) using the oral 14(R,S)-[18F]-fluoro-6-thia-heptadecanoic acid positron emission tomography method after 7 days of an ISOCAL diet versus a LOWCAL diet using a randomized crossover design.

Selective Impairment of Glucose but Not Fatty Acid or Oxidative Metabolism in Brown Adipose Tissue of Subjects With Type 2 Diabetes.

Spontaneous glucose uptake by brown adipose tissue (BAT) is lower in overweight or obese individuals and in diabetes. However, BAT metabolism has not been previously investigated in patients with type 2 diabetes during controlled cold exposure. Using positron emission tomography with (11)C-acetate, (18)F-fluoro-deoxyglucose ((18)FDG), and (18)F-fluoro-thiaheptadecanoic acid ((18)FTHA), a fatty acid tracer, BAT oxidative metabolism and perfusion and glucose and nonesterified fatty acid (NEFA) turnover were determined in men with well-controlled type 2 diabetes and age-matched control subjects under experimental cold exposure designed to minimize shivering.

Effect of Sex and Impaired Glucose Tolerance on Organ-Specific Dietary Fatty Acid Metabolism in Humans.

Oral 14(R,S)-[(18)F]-fluoro-6-thia-heptadecanoic acid was used to determine whether an increase in cardiac dietary fatty acid (DFA) metabolism in impaired glucose tolerance (IGT) is different in men and women. Myocardial DFA partitioning after 6 h was higher in IGT versus control subjects (P = 0.006) in both men (2.

Improved cardiac function and dietary fatty acid metabolism after modest weight loss in subjects with impaired glucose tolerance.

Using a novel positron emission tomography (PET) method with oral administration of 14(R,S)-[¹⁸F]-fluoro-6-thia-heptadecanoic acid (¹⁸FTHA), we recently demonstrated that subjects with impaired glucose tolerance (IGT) display an impairment in cardiac function associated with increased myocardial uptake of dietary fatty acids. Here, we determined whether modest weight loss induced by lifestyle changes might improve these cardiac metabolic and functional abnormalities. Nine participants with IGT, enrolled in a one-year lifestyle intervention trial, were invited to undergo determination of organ-specific postprandial dietary fatty acids partition using the oral ¹⁸FTHA method, and cardiac function and oxidative metabolic index using PET [¹¹C]acetate kinetics with ECG-gated PET ventriculography before and after the intervention.

Increased brown adipose tissue oxidative capacity in cold-acclimated humans.

Context: Recent studies examining brown adipose tissue (BAT) metabolism in adult humans have provided convincing evidence of its thermogenic potential and role in clearing circulating glucose and fatty acids under acute mild cold exposure. In contrast, early indications suggest that BAT metabolism is defective in obesity and type 2 diabetes, which may have important pathological and therapeutic implications. Although many mammalian models have demonstrated the phenotypic flexibility of this tissue through chronic cold exposure, little is known about the metabolic plasticity of BAT in humans.