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Comprehensive plasma acylcarnitine profiles of type 2 diabetic and non‐diabetic subjects with or without an uncoupling protein 3 (UCP3) missense polymorphism
Author(s) -
Adams Sean H.,
Hoppel Charles L.,
Lok Kerry H.,
Newman John W.,
Garvey W. Timothy
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.614.15
Subject(s) - endocrinology , medicine , ucp3 , insulin resistance , biology , type 2 diabetes , type 2 diabetes mellitus , chemistry , insulin , diabetes mellitus , uncoupling protein , obesity , brown adipose tissue
Type 2 diabetes mellitus (T2DM) is often correlated with reduced muscle fatty acid combustion in the fasted state. This may be due to dysfunctional mitochondrial activity and accumulation of specific lipid metabolites implicated in insulin resistance. Biomarkers of muscle fat combustion would be valuable to identify persons at‐risk for developing T2DM and to better understand muscle intermediary metabolism. To address this, we compared >40 individual plasma acylcarnitines in overnight‐fasted adult women harboring a UCP3 premature‐stop allele (50% lower whole‐body fat combustion, apparently due to limited muscle UCP3 activity) to a control cohort. Contrary to expectations, acylcarnitine profiles did not differ by genotype. However, across genotypes, T2DM subjects (n=44) displayed (relative to non‐diabetics, n=12): ~50% increased total acylcarnitines (6.52 ± 0.32 vs. 4.40 ± 0.55 μM; p<0.01), ~60% higher acetylcarnitine (5.35 ± 0.29 vs. 3.40 ± 0.46 μ p<0.01), and ~37% decreased propionylcarnitine (0.24 ± 0.02 vs. 0.38 ± 0.04 μ p<0.001). Such patterns are consistent with a hypothetical model in which fasted T2DM tissues (a) have inordinately low availability of propionyl‐CoA (a component of TCA cycle‐replenishing [anaplerotic] reactions), and (b) increased pools of pyruvate‐derived acetyl‐CoA, presumably due to relatively elevated glycolysis and/or reduced TCA cycle acetyl‐CoA consumption.