Abstract
Induction of heme oxygenase-1 (HO-1) has been demonstrated to decrease body weight and improve insulin sensitivity in several models of obesity in rodents. To further study the role of HO-1 in adipose tissue, we created an adipose-specific HO-1 knockout mouse model. Male and female mice were fed either a control or a high-fat diet for 30 weeks. Body weights were measured weekly and body composition, fasting blood glucose and insulin levels were determined every six weeks. Adipocyte-specific knockout of HO-1 had no significant effect on body weight in mice fed a high-fat diet but increased body weight in female mice fed a normal-fat diet. Although body weights were not different in females fed a high fat diet, loss of HO-1 in adipocytes resulted in significant alterations in body composition. Adipose-specific HO-1 knockout resulted in increased fasting hyperglycemia and insulinemia in female but not male mice on both diets. Adipose-specific knockout of HO-1 resulted in a significant loss of HO activity and a decrease in the protein levels of adiponectin in adipose tissue. These results demonstrate that loss of HO-1 in adipocytes has greater effects on body fat and fasting hyperglycemia in a sex-dependent fashion and that expression of HO-1 in adipose tissue may have a greater protective role in females as compared to males.
Highlights
Obesity continues to be a significant health concern in the United States and globally
We utilized a novel model of adipose-specific knockout of heme oxygenase-1 (HO-1) to determine its role in the regulation of body weight, composition and fasting blood glucose and insulin levels
We crossed Flox Heme oxygenase (HO)-1 mice with mice expressing the Cre recombinase under the control of the adiponectin promoter to achieve adipocyte-specific deletion of HO-1
Summary
Obesity continues to be a significant health concern in the United States and globally. The results of the present study demonstrate that loss of adipocyte HO-1 has significant effects on body composition to increase fat mass and lower lean mass independent of any changes in total body weight These alterations in body composition in female adipocyte-specific HO-1 KO mice are associated with increased insulin resistance exhibited by increased fasting blood glucose and insulin levels in mice fed both normal and high-fat diets. These results suggest that adipose HO-1 may play a greater protective role to preserve insulin sensitivity in females versus males. These experiments are beyond the scope of the current study and would require additional studies in this model
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