α-Lipoic acid: physiologic mechanisms and indications for the treatment of metabolic syndrome

Abstract

In animal experiments, the potent antioxidant and free radical scavenger α-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 α-lipoic acid can affect central and peripheral modulation of 5′-AMP-activated protein kinase, activate PPAR-α and PPAR-γ, modulate PPAR-regulated genes and upregulate the expression of PPAR-γ mRNA and protein in cardiac tissue and aorta smooth muscle. To a large extent, these findings can explain the observed beneficial metabolic effects of α-lipoic acid, supporting its potential application as a therapeutic agent for the treatment of the metabolic syndrome.

Keywords::

• α-lipoic acid
• AMP kinase
• antioxidant
• dyslipidemia
• hypertension
• insulin resistance
• lipotoxicity
• metabolic syndrome
• obesity
• oxidative stress
• peroxisome proliferator-activated receptors
• PPAR-γ
• Type 2 diabetes
• weight loss

Disclosure

HA Pershadsingh was supported by National Institutes of Health grant 2R42AR44767-02A2 and a grant from Bethesda Pharmaceuticals. HA Pershadsingh owns stock in Bethesda Pharmaceuticals.

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