| Summary: | Developmental genes are important regulators of fat distribution and adipose tissue (AT) function. In humans, the expression of homeobox c9 (<i>HOXC9</i>) is significantly higher in subcutaneous compared to omental AT and correlates with body fat mass. To gain more mechanistic insights into the role of <i>Hoxc9</i> in AT, we generated <i>Fabp4</i>-Cre-mediated <i>Hoxc9</i> knockout mice (AT<i>Hoxc9</i><sup>-/-</sup>). Male and female AT<i>Hoxc9</i><sup>-/-</sup> mice were studied together with littermate controls both under chow diet (CD) and high-fat diet (HFD) conditions. Under HFD, only male AT<i>Hoxc9</i><sup>-/-</sup> mice gained less body weight and exhibited improved glucose tolerance. In both male and female mice, body weight, as well as the parameters of glucose metabolism and AT function were not significantly different between AT<i>Hoxc9</i><sup>-/- </sup>and littermate control CD fed mice. We found that crossing <i>Hoxc9</i> floxed mice with <i>Fabp4</i>-Cre mice did not produce a biologically relevant ablation of <i>Hoxc9</i> in AT. However, we hypothesized that even subtle reductions of the generally low AT <i>Hoxc9</i> expression may cause the leaner and metabolically healthier phenotype of male HFD-challenged AT<i>Hoxc9</i><sup>-/-</sup> mice. Different models of in vitro adipogenesis revealed that <i>Hoxc9</i> expression precedes the expression of <i>Fabp4</i>, suggesting that ablation of <i>Hoxc9</i> expression in AT needs to be achieved by targeting earlier stages of AT development.
|
|---|
