Lack of AKT in adipocytes causes severe lipodystrophy

• AKT-action and insulin signaling are required in an adipocyte-autonomous fashion to maintain adipose tissue stores.
• Mice with adipocyte-specific loss of Akt1 and Akt2 display a nearly complete loss of white and brown adipose tissue.
• These lipodystrophic mice have organomegaly, perturbed glucose homeostasis and insulin resistance.

ObjectiveAdipose depot mass is tightly regulated to maintain energy homeostasis. AKT is a critical kinase in the insulin-signaling cascade that is required for the process of adipogenesis in vitro. However, the role of AKT in the maintenance and/or function of mature adipocytes in vivo had not been examined.MethodsTo study this, we deleted Akt1 and Akt2 in adipocytes of mice using the AdipoQ-Cre driver.ResultsStrikingly, mice lacking adipocyte AKT were severely lipodystrophic, having dramatically reduced gonadal adipose and no discernible subcutaneous or brown adipose tissue. As a result, these mice developed severe insulin resistance accompanied by fatty liver, hepatomegaly and with enlarged islets of Langerhans.ConclusionsThese data reveal the critical role of adipocyte AKT and insulin signaling for maintaining adipose tissue mass.