Sex-Dependent Effects of HO-1 Deletion from Adipocytes in Mice

Int J Mol Sci. 2017 Mar 11;18(3):611. doi: 10.3390/ijms18030611.


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.

Keywords: Cre recombinase; adiponectin; bilirubin; diabetes; insulin resistance; obesity.

MeSH terms

  • Adipocytes / metabolism*
  • Adiponectin / metabolism
  • Adipose Tissue / metabolism
  • Alleles
  • Animals
  • Biomarkers
  • Blood Glucose
  • Body Composition / genetics
  • Body Weight
  • Diet, High-Fat
  • Enzyme Activation
  • Fasting
  • Female
  • Gene Targeting
  • Heme Oxygenase-1 / deficiency*
  • Heme Oxygenase-1 / metabolism
  • Hyperinsulinism / blood
  • Hyperinsulinism / genetics
  • Inflammation Mediators / metabolism
  • Insulin Resistance / genetics
  • Male
  • Mice
  • Mice, Knockout
  • Obesity
  • Organ Specificity / genetics
  • Sex Factors


  • Adiponectin
  • Biomarkers
  • Blood Glucose
  • Inflammation Mediators
  • Heme Oxygenase-1