Effect of R(+)alpha-lipoic acid on pyruvate metabolism and fatty acid oxidation in rat hepatocytes.
Effect of R(+)alpha-lipoic acid on pyruvate metabolism and fatty acid oxidation in rat hepatocytes.
复制标题
R( )α-硫辛酸对大鼠肝细胞丙酮酸代谢和脂肪酸氧化的影响。
DOI：
10.1016/j.metabol.2003.09.008
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Buse,MariaG
中科院分区：
文献类型：
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作者：
Walgren,JennieL;Amani,Zainab;McMillan,JoEllynM;Locher,Mathias;Buse,MariaG
R-(+)-α-lipoic acid (R-LA) is the naturally occuring enantiomer of LA. It is a strong antioxidant and cofactor of key metabolic enzyme complexes catalyzing the decarboxylation of α-keto acids. Racemic LA (rac-LA) has shown promise in treating diabetic polyneuropathy, and some studies suggest that it improves glucose homeostasis in patients with type 2 diabetes. We examined the effects of R-LA on pyruvate metabolism and free fatty acid (FFA) oxidation in primary cultured hepatocytes isolated from 24-hour fasted rats. After overnight culture in serum-free medium, cells were pre-exposed to R-LA for 3 hours before assays. R-LA (25 to 200 μmol/L) significantly increased pyruvate oxidation (∼2-fold at the highest dose tested) measured as14CO2production from [1-14C]pyruvate by the cells over 1 hour post-treatment. These effects correlated with proportional, significant increases in the activation state of the pyruvate dehydrogenase (PDH) complex. R-LA treatment inhibited glucose production from pyruvate by approximately 50% at 50 μmol/L R-LA and approximately 90% at 200 μmol/L. Palmitate oxidation was measured in hepatocytes cultured in the presence of albumin and physiological (0.1 mmol/L) or high (1.5 mmol/L) concentrations of FFA. The latter markedly enhanced FFA oxidation. R-LA treatment significantly inhibited FFA oxidation in both media, but was more effective in high FFA, where it reduced FFA oxidation by 48% to 82% at 25 to 200 μmol/L, respectively. Identical doses of R-LA did not affect FFA oxidation by L6 myotubes (a cell culture model for skeletal muscle) in either high or low FFA medium, but enhanced pyruvate oxidation. In conclusion, 3-hour exposure of primary cultured rat hepatocytes to R-LA at therapeutically relevant concentrations increased pyruvate oxidation, apparently by activation of the PDH complex, and decreased gluconeogenesis and FFA oxidation. These features may prove useful in the control of type 2 diabetes.
