Amelioration of Lipid Abnormalities by α-Lipoic acid Through Antioxidative and Anti-Inflammatory Effects
Open Access
- 1 August 2011
- Vol. 19 (8), 1647-1653
- https://doi.org/10.1038/oby.2011.121
Abstract
Recent data have revealed that oxidative products and inflammatory mediators are increased in the insulin‐resistant states of obesity and type 2 diabetes mellitus (T2DM). Obese patients with impaired glucose tolerance (IGT) are at high risk for developing T2DM and have high incidence of dyslipidemia. α‐Lipoic acid (ALA) is a potent antioxidant with insulin sensitizing activity. However, it is not clear whether ALA is effective on lipid parameters in humans. This study has investigated 22 obese subjects with IGT (obese‐IGT), 13 of whom underwent 2‐week ALA treatment, 600 mg intravenously once daily. Before and after the treatment, euglycemic‐hyperinsulinemic clamps were used to measure insulin sensitivity. Meanwhile, plasma lipids, oxidative products, and chronic inflammatory markers were measured. After treatment of ALA in obese‐IGT patients, insulin sensitivity was improved, insulin sensitivity index (ISI) impressively enhanced by 41%. Plasma levels of free fatty acids (FFAs), triglyceride (TG), total cholesterol (T‐Chol), low density lipoprotein‐cholesterol (LDL‐Chol), small dense LDL‐Chol (sd‐LDL), oxidized LDL‐Chol (ox‐LDL‐Chol), very low density lipoprotein‐cholesterol (VLDL‐Chol) were all significantly decreased (P < 0.01). At the same time, both plasma oxidative products (malondialdehyde (MDA), 8‐iso‐prostaglandin) and inflammatory markers (tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6)) were remarkably decreased (P < 0.01), while adiponectin was increased (P < 0.01). There are significant negative correlations between ISI and plasma FFAs, sd‐LDL‐Chol, ox‐LDL‐Chol, MDA, 8‐iso‐prostaglandin, TNF‐α, and IL‐6, and positive correlations with HDL‐Chol and adiponectin in obese‐IGT patients. The results indicate that short‐term treatment with ALA can improve insulin sensitivity and plasma lipid profile possibly through amelioration of oxidative stress and chronic inflammatory reaction in obese patients with IGT.Keywords
This publication has 39 references indexed in Scilit:
- Lipoic acid improves hypertriglyceridemia by stimulating triacylglycerol clearance and downregulating liver triacylglycerol secretionArchives of Biochemistry and Biophysics, 2009
- Interactions of the advanced glycation end product inhibitor pyridoxamine and the antioxidant α-lipoic acid on insulin resistance in the obese Zucker ratMetabolism, 2008
- Association Between Circulating Oxidized Low-Density Lipoprotein and Incidence of the Metabolic SyndromeJama-Journal Of The American Medical Association, 2008
- Lipid Lowering Effect of Antioxidant Alpha-Lipoic Acid in Experimental AtherosclerosisJournal of Clinical Biochemistry and Nutrition, 2008
- α-Lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscleBiochemical and Biophysical Research Communications, 2005
- The Molecular Basis for Oxidative Stress-Induced Insulin ResistanceAntioxidants and Redox Signaling, 2005
- Macrophage-derived lipoprotein lipase increases aortic atherosclerosis in cholesterol-fed Tg rabbitsAtherosclerosis, 2005
- Bcl-2 in endothelial cells is increased by vitamin E and α-lipoic acid supplementation but not exercise trainingJournal of Molecular and Cellular Cardiology, 2005
- Low-Density Lipoprotein Subfractions and the Long-Term Risk of Ischemic Heart Disease in MenArteriosclerosis, Thrombosis, and Vascular Biology, 2005
- Irbesartan and Lipoic Acid Improve Endothelial Function and Reduce Markers of Inflammation in the Metabolic SyndromeCirculation, 2005