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

Abstract

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

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

“…We previously found that subjects with IGT display an increase in myocardial DFA uptake that is associated with decreased left ventricular function (14,22), an abnormality that was corrected by modest weight loss after a 1-year individually tailored lifestyle intervention (15). Here, we found that the improvement of insulin resistance with a 7-day hypocaloric, low-SFA diet did not change early 2-h postprandial myocardial DFA uptake in subjects with IGT.…”

“…Despite the small number of participants, the a priori power of our study for most outcomes ranged between 70% and 95%. The small number of men and women limits our power to detect sex differences in the contribution of adipose tissues versus direct chylomicron-TG uptake to cardiac DFA partitioning (22). Another limitation of our study is that the PET ventriculography method may not be as sensitive as cardiac MRI or echocardiography to detect changes in left ventricular diastolic function.…”

Hypertriglyceridemia Associated With Abdominal Obesity

“…10 The small number of women is also a limitation given that sex is an important determinant of VLDL metabolism in healthy subjects. 3 In addition, there is a marked sexual dichotomy in cardiac and adipose tissue-specific chylomicron fatty acid uptake in subjects with impaired glucose tolerance, 18 suggesting that sex may influence…”

“…The selection criteria and absence of healthy controls may, however, have favored a stronger correlation between apoCIII levels and VLDL 1 kinetics compared with other lipoproteins, such as apolipoprotein E given that apoCIII-rich VLDL secretion is increased in hypertriglyceridemic individuals. 10 The small number of women is also a limitation given that sex is an important determinant of VLDL metabolism in healthy subjects.3 In addition, there is a marked sexual dichotomy in cardiac and adipose tissue-specific chylomicron fatty acid uptake in subjects with impaired glucose tolerance, 18 suggesting that sex may influence More mechanistic studies are clearly needed on these important sex-related differences in triglyceride metabolism. The study by Borén et al contributes to the remarkable and rapid recent advances in our understanding of the factors leading to hypertriglyceridemia associated with abdominal obesity.…”

“…3 In addition, there is a marked sexual dichotomy in cardiac and adipose tissue-specific chylomicron fatty acid uptake in subjects with impaired glucose tolerance, 18 suggesting that sex may influence More mechanistic studies are clearly needed on these important sex-related differences in triglyceride metabolism. The study by Borén et al contributes to the remarkable and rapid recent advances in our understanding of the factors leading to hypertriglyceridemia associated with abdominal obesity.…”