Adipocyte PFKFB3 overexpression protects mice from diet‐induced adipose tissue inflammation and systemic insulin resistance

While adipose tissue inflammation critically contributes to the development of overnutrition‐related systemic insulin resistance, adiposity does not necessarily result in adipose tissue inflammation and does not always bring about systemic insulin resistance. In adipocytes, PFKFB3 is a master regulator that links fuel metabolism and inflammatory response. To define a direct role for adipocyte PFKFB3 in regulating adiposity and systemic insulin sensitivity, mice with selective PFKFB3 overexpression in adipocytes (Adi‐PFKFB3TG) were generated using an aP2‐PFKFB3 fusion gene. On a high fat‐diet, Adi‐PFKFB3TG mice gained much more weight than wild‐type mice. This was attributed to a greater increase in adiposity in Adi‐PFKFB3TG mice than in wild‐type controls. However, Adi‐PFKFB3TG mice exhibited decreased severity of HFD‐induced adipose tissue dysfunction, as evidenced by increased insulin signaling and decreased levels of proinflammatory cytokines. Furthermore, at the whole body level, Adi‐PFKFB3TG mice did not display HFD‐induced systemic insulin resistance as did wild‐type controls. Together, these data suggest that the PFKFB3 in adipocytes protects against diet‐induced insulin resistance and adipose tissue inflammatory response while stimulating adiposity. Grant Funding Source : ADA Junior Faculty Award