Hosick Peter A, Weeks Mary Frances, Hankins Michael W, Moore Kyle H, Stec David E
Department of Physiology & Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216, USA.
Department of Exercise Science and Physical Education, Montclair State University, Montclair, NJ 07043, USA.
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.
在啮齿动物的几种肥胖模型中，血红素加氧酶-1（HO-1）的诱导已被证明可降低体重并改善胰岛素敏感性。为了进一步研究HO-1在脂肪组织中的作用，我们创建了一种脂肪特异性HO-1基因敲除小鼠模型。雄性和雌性小鼠分别喂食对照饮食或高脂饮食30周。每周测量体重，每六周测定身体组成、空腹血糖和胰岛素水平。HO-1的脂肪细胞特异性敲除对喂食高脂饮食的小鼠体重没有显著影响，但增加了喂食正常脂肪饮食的雌性小鼠的体重。虽然喂食高脂饮食的雌性小鼠体重没有差异，但脂肪细胞中HO-1的缺失导致身体组成发生显著变化。脂肪特异性HO-1基因敲除导致两种饮食下雌性而非雄性小鼠空腹血糖和胰岛素血症增加。脂肪特异性敲除HO-1导致脂肪组织中HO活性显著丧失和脂联素蛋白水平降低。这些结果表明，脂肪细胞中HO-1的缺失以性别依赖的方式对体脂和空腹血糖产生更大影响，并且与雄性相比，脂肪组织中HO-1的表达在雌性中可能具有更大的保护作用。
