(The FASEB Journal. 2008;22:lb642)
© 2008 FASEB
Treatment of Obese Diabetic Mice with an Heme Oxygenase Inducer Reduces Visceral and Abdominal Adiposity, Increases Adiponectin Levels and Improves Insulin Sensitivity and Glucose Tolerance
Ming Li,
Dong Hyun Kim,
Francesco Piccolomini,
Luca Vanella and
Nader G. Abraham
Pharmacology, New York Medical College, Valhalla, NY
ABSTRACT
Objective: We hypothesized that the induction of heme oxygenase-1 (HO-1) and increased HO activity would ameliorate insulin resistance and type 2 diabetes. Methods and Results: Lean and obese mice were administered the HO-1 inducer CoPP (3 mg/kg) with and without the HO inhibitor SnMP once a week for 6 weeks. Body weight, blood glucose and serum cytokines and adiponectin were measured. HO activity was reduced in ob mice compared to lean mice. Administration of CoPP caused a sustained increase in HO-1 protein, prevented weight gain, decreased visceral and subcutaneous fat content (p<0.03 and p<0.01 respectively compared to vehicle animals), increased serum adiponectin and decreased plasma TNF
, IL-6 and IL-1β levels (p<0.05). HO-1 induction improved insulin sensitivity and glucose tolerance and decreased insulin levels. HO-1 expression decreased adipogenesis in bone marrow in vivo and increased adiponectin levels in the culture media. Conclusions: This study provides strong evidence for the existence of an HO-1-adiponectin regulatory axis that can be manipulated to ameliorate the deleterious effects of obesity and the metabolic syndrome associated with cardiovascular disease and diabetes.
