Treatment of obese diabetic mice with a heme oxygenase inducer reduces visceral and subcutaneous adiposity, increases adiponectin levels, and improves insulin sensitivity and glucose tolerance.

Description

In order to identify novel therapeutic agents that could have an impact on fat distribution and insulin sensitivity, Li et al. hypothesized that targeting the heme oxygenase (HO) system could improve insulin sensitivity in obese and lean mice. Given the fact that induction of the HO system has previously been shown to increase arterial antioxidative enzymes and vasoprotection in diabetic rats and mice, they sought to investigate whether inducing HO-1 and increasing HO activity would improve markers of insulin sensitivity and inflammation as well as fat distribution. For that purpose, they performed intraperitoneal injections in lean and obese (B6v-Lep ob/J) mice of the HO-1 inducer cobalt protoporphyrin (3 mg/kg CoPP) once a week for 6 weeks. The effect of CoPP in inducing HO activity was higher in obese vs. lean mice. Compared to obese vehicle animals, obese CoPP-treated mice had increased HO-1 protein and serum adiponectin. Administration of CoPP also significantly reduced visceral and subcutaneous fat content as well as serum levels of tumor necrosis factor-a, interleukin-6, and interleukin-1β, without a significant decrease in food intake. A 120-minute intraperitoneal glucose tolerance test and a 90-minute intraperitoneal insulin sensitivity test were also performed. In both tests, glucose levels appeared to be lower in obese mice treated with CoPP compared to obese mice treated with vehicle. This study provides evidence for an important role of the HO-1-adiponectin axis. Based on the results, the authors concluded that targeting this pathway could counteract the effects of obesity and the metabolic syndrome.