Lack of AKT in adipocytes causes severe lipodystrophy

Objective: Adipose 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. Methods: To study this, we deleted Akt1 and Akt2 in adipocytes of mice using the AdipoQ-Cre driver. Results: Strikingly, 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. Conclusions: These data reveal the critical role of adipocyte AKT and insulin signaling for maintaining adipose tissue mass. Author Video: Author Video Watch what authors say about their articles Keywords: Akt, Lipodystrophy, Insulin signaling, Insulin resistanc

Akt2 and SGK3 are both determinants of postnatal hair follicle development

SGK3, which previously has been shown to play a key role in hair follicle development in mice, is a member of the AGC family of serine-threonine kinases. Mice lacking SGK3 have abnormal follicle cycling, which begins shortly after birth and ameliorates substantially with age. However, this developmental abnormality is not recapitulated in mice lacking closely related kinases Akt1, Akt2, or Akt3. To examine whether Akt2 interacts with SGK3 in postnatal hair development, we have generated and characterized Akt2/SGK3 double knockouts (DKOs). We find that the DKO mice have a defect in hair growth that is markedly worse than that of SGK3−/− mice and does not ameliorate with age. Morphologically, this defect is characterized by accelerated entry into catagen and through anagen, irregular hair follicle orientation, and increased expression of sebaceous glands. The defect is preceded by a profound failure to increase follicle matrix cell nuclear β-catenin accumulation and proliferation at the onset of morphogenesis. Furthermore, in cultured keratinocytes, transfected Akt2 and SGK3 both stimulate transcription of a β-catenin-LEF1-dependent reporter gene. Thus, SGK3 and Akt2 both appear to play important roles in postnatal hair follicle morphogenesis, likely because of their redundant regulation of β-catenin-dependent transcriptional processes, which control hair follicle cell proliferation.—Mauro, T. M., McCormick, J. A., Wang, J., Boini, K. M., Ray, L., Monks, B., Birnbaum, M. J., Lang, F., and Pearce, D. Akt2 and SGK3 are both determinants of postnatal hair follicle development