title: Differential function of Akt1 and Akt2 in human adipocytes.
abstract: Adipose tissue mass is determined by both cell size and cell number. Mouse models suggest that Akt isoforms are involved in the determination of fat mass by interfering with preadipocyte-to-adipocyte transition and regulating lipid storage. Here, we took advantage of a lentiviral mediated shRNA approach to study the role of Akt1 and Akt2 in differentiation and metabolism of human SGBS adipocytes. Adipogenic differentiation as measured by lipid accumulation was robustly inhibited in Akt2 deficient cells, whereas it was not affected by knockdown of Akt1. The knockdown of Akt2 caused an almost complete inhibition of preadipocyte proliferation. Furthermore, Akt2 deficient preadipocytes were significantly more sensitive to apoptosis induction by death receptor stimulation compared to Akt1 deficient cells. Both the knockdown of Akt1 or Akt2 equally affected insulin-stimulated lipogenesis as well as the anti-lipolytic effect of insulin. We conclude that Akt2 is indispensable for the regulation of preadipocyte and adipocyte number, whereas Akt1 and Akt2 are equally important for the regulation of insulin-stimulated metabolic pathways in human adipocytes. Recently proposed as an attractive target for the treatment of cancer, modulating Akt2 activity might also be a new molecular strategy to control adipose tissue mass.
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Eythstr. 24, 89075 Ulm, Germany.
authors.forename: Pamela
authors.initials: P
authors.lastname: Fischer-Posovszky
authors.forename: Daniel
authors.initials: D
authors.lastname: Tews
authors.forename: Sina
authors.initials: S
authors.lastname: Horenburg
authors.forename: Klaus-Michael
authors.initials: KM
authors.lastname: Debatin
authors.forename: Martin
authors.initials: M
authors.lastname: Wabitsch
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D050156:Adipogenesis; D000273:Adipose Tissue / Q000378:metabolism; D002452:Cell Count; D002460:Cell Line; D049109:Cell Proliferation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis; D050155:Lipogenesis; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D007328:Insulin; D008055:Lipids; D034741:RNA, Small Interfering; C494918:AKT1 protein, human; C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose