Several anti-diabetic drugs exert beneficial effects for metabolic syndrome by inhibiting mitochondrial function. Although much progress has been made toward understanding the roles of mitochondrial function modulators in treating metabolic diseases, the potential effects of inhibitor on mitochondrial respiratory chain complex III remain unclear.

The research group led by Prof. LI Jia in Shanghai Institute of Materia Medica, Chinese Academy of Sciences investigated the metabolic effects of azoxystrobin (AZOX), a Q inhibitor of complex III in the high-fat diet-fed mouse model with insulin resistance to elucidate the mechanism by which AZOX improves glucose and lipid metabolisms at the metabolic cellular level.

In this study, AZOX was used to evaluate the therapeutic potential of mitochondria Q site of complex III inhibitors for overnutrition-related metabolic diseases. Researchers demonstrated that AZOX treatment improved insulin sensitivity in a rodent model of diet-induced obesity, reduced whole-body adiposity, and shifted energy substrate preference away from the use of fatty acid, a favorable adjustment for disorders characterized by glucose intolerance.

Some of the effects of AZOX were, at least partially mediated by activating the crucial cell-intrinsic energy sensor, AMP-activated protein kinase (AMPK). AZOX, a Q inhibitor of mitochondrial respiratory complex III, exerts whole-body beneficial effects on the regulation of glucose and lipid homeostasis in high-fat diet-fed mice. These findings provide evidence that a Q inhibitor of mitochondrial respiratory complex III represents a novel approach for treatment of obesity.

This work has been published on Biochimica et biophysica acta-General Subject (2014, 1840(7): 2212-21)

Full text: http://www.ncbi.nlm.nih.gov/pubmed/24726979.

（Image by SIMM）

(Source:LI Jia’s Group)