Alpha-lipoic acid: physiologic mechanisms and indications for the treatment of metabolic syndrome.
In animal experiments, the potent antioxidant and free radical scavenger alpha-lipoic acid has been shown to cause weight loss, ameliorate insulin resistance and atherogenic dyslipidemia, as well as to lower blood pressure, all of these being components of the metabolic syndrome. Recent investigations on its mechanisms of action indicate that alpha-lipoic acid can affect central and peripheral modulation of 5'-AMP-activated protein kinase, activate PPAR-alpha and PPAR-gamma, modulate PPAR-regulated genes and upregulate the expression of PPAR-gamma mRNA and protein in cardiac tissue and aorta smooth muscle. To a large extent, these findings can explain the observed beneficial metabolic effects of alpha-lipoic acid, supporting its potential application as a therapeutic agent for the treatment of the metabolic syndrome.
Pershadsingh
Harrihar A
HA
Bethesda Pharmaceuticals, Inc., 404 Windsor Park Drive, Bakersfield, California 93311, USA. hpershad@UCI.edu
D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D006801:Humans; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000378:metabolism; D047493:PPAR alpha / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology* / Q000627:therapeutic use
D000975:Antioxidants; D047493:PPAR alpha; D047495:PPAR gamma; D008063:Thioctic Acid; C118888:AMP-dependent kinase (ATP-forming); D017856:Phosphotransferases (Phosphate Group Acceptor)