Reciprocal effects of α-lipoic acid on adenosine monophosphate-activated protein kinase activity in obesity induced by ovariectomy in rats

Objective: Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays an important role in regulating whole-body energy homeostasis. The aim of this study was to investigate dietary alpha-lipoic acid (alpha-LA) supplementation on the activation of AMPK in both central and peripheral tissues in obese rats induced by ovariectomy. Methods: Ovariectomized (Ovx) rats were treated with alpha-LA (200 mg/kg) 3 to 10 weeks after surgery. Body weight, food intake, fat mass, phosphorylated AMPK alpha (pAMPK alpha), and phosphorylated acetyl-CoA carboxylase (ACC) protein expression in both the hypothalamus and white adipose tissue (WAT) as well as plasma leptin and adiponectin levels were measured in rats after either Ovx or sham operations. Results: Compared with control rats, ovariectomy led to increased body weight, food intake, and WAT mass 2 to 10 weeks after surgery. Furthermore, plasma leptin and adiponectin levels as well as hypothalamic pAMPK alpha expression were significantly increased after ovariectomy, accompanied by a reduction in pAMPK alpha expression in WAT after ovariectomy. However, after treatment with alpha-LA, the elevation of leptin and adiponectin levels and the activation of hypothalamic AMPK alpha and ACC, as induced by ovariectomy, were significantly suppressed. Meanwhile, decreased fat mass and increased pAMPK alpha and phosphorylated ACC expression in the WAT were observed in Ovx rats treated with alpha-LA. Conclusions: alpha-LA significantly decreased appetite and fat accumulation, possibly through the regulation of central and peripheral AMPK activities in rats. Therefore, this study provides a rationale for the therapeutic use of alpha-LA for obesity in postmenopausal women.