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.Objective:Our objective was to determine whether 4 weeks of daily cold exposure could increase both the volume of metabolically active BAT and its oxidative capacity.Design:Six nonacclimated men were exposed to 10°C for 2 hours daily for 4 weeks (5 d/wk), using a liquid-conditioned suit. Using electromyography combined with positron emission tomography with [11C]acetate and [18F]fluorodeoxyglucose, shivering intensity and BAT oxidative metabolism, glucose uptake, and volume before and after 4 weeks of cold acclimation were examined under controlled acute cold-exposure conditions.Results:The 4-week acclimation protocol elicited a 45% increase in BAT volume of activity (from 66 ± 30 to 95 ± 28 mL, P < .05) and a 2.2-fold increase in cold-induced total BAT oxidative metabolism (from 0.725 ± 0.300 to 1.591 ± 0.326 mL·s−1, P < .05). Shivering intensity was not significantly different before compared with after acclimation (2.1% ± 0.7% vs 2.0% ± 0.5% maximal voluntary contraction, respectively). Fractional glucose uptake in BAT increased after acclimation (from 0.035 ± 0.014 to 0.048 ± 0.012 min−1), and net glucose uptake also trended toward an increase (from 163 ± 60 to 209 ± 50 nmol·g−1·min−1).Conclusions:These findings demonstrate that daily cold exposure not only increases the volume of metabolically active BAT but also increases its oxidative capacity and thus its contribution to cold-induced thermogenesis.
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 , 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. Despite smaller volumes of 18 FDG-positive BAT and lower glucose uptake per volume of BAT compared with young healthy control subjects, cold-induced oxidative metabolism and NEFA uptake per BAT volume and an increase in total body energy expenditure did not differ in patients with type 2 diabetes or their age-matched control subjects. The reduction in 18 FDG-positive BAT volume and BAT glucose clearance were associated with a reduction in BAT radiodensity and perfusion. 18 FDG-positive BAT volume and the cold-induced increase in BAT radiodensity were associated with an increase in systemic NEFA turnover. These results show that cold-induced NEFA uptake and oxidative metabolism are not defective in type 2 diabetes despite reduced glucose uptake per BAT volume and BAT "whitening."
Carpentier AC. Improved cardiac function and dietary fatty acid metabolism after modest weight loss in subjects with impaired glucose tolerance.
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 (2.14 [95% CI sex difference. Men had higher net myocardial DFA uptake between time 90 and 120 min driven by higher chylomicrontriglyceride (TG) levels. IGT-associated increased cardiac DFA partitioning was directly related to obesity in women, whereas it was associated with IGT per se in men. We conclude that early cardiac DFA uptake is higher in men driven by change in postprandial chylomicron-TG level but that increase in 6-h postprandial cardiac DFA partitioning nevertheless occurs with IGT both in men and women.Sex, obesity, and insulin resistance appear to act independently but also in concert on myocardial metabolism, structure, and function. Studies conducted in the fasting state show that women have greater myocardial oxygen consumption (1), which increases with obesity (2). In addition, female sex appears to be an important predictor of higher diabetes-associated cardiac plasma nonesterified fatty acid (NEFA) utilization (3). Excess exposure of lean tissues to fatty acids may stem from a disordered storage of dietary fatty acids (DFAs) in adipocytes (4-7). We recently developed a novel method for noninvasive measurement of organ-specific DFA uptake and partitioning using 14(R,S)-[ 8). Using this method, we found that subjects with impaired glucose tolerance (IGT) displayed increased myocardial DFA partitioning and fractional uptake that correlated negatively with left ventricular ejection fraction (9). Subjects with IGT also displayed reduced DFA partitioning in abdominal adipose tissues (9), in accordance with findings using conventional tracer methods (10-12).Due to the small sample size at the time of our previous report, it was not possible to assess whether any sexrelated differences in organ-specific DFA metabolism were present and could modulate the effect of IGT on cardiac metabolism. Based on previous reports on cardiac NEFA metabolism (3), the hypothesis of the current study was that elevated DFA uptake and partitioning observed with IGT would be worsened in women versus men. A secondary exploratory objective of our study was to determine sexrelated differences in liver, skeletal muscle, and adipose tissue DFA partitioning according to IGT status. RESEARCH DESIGN AND METHODS Study ParticipantsForty-one Caucasian individuals (see Table 1) with normal (IGT 2 ) and IGT (IGT + ), defined as having a 2-h post 75-g
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