Rapid depot-specific activation of adipocyte precursor cells at the onset of obesity.
Excessive accumulation of white adipose tissue (WAT) is the defining characteristic of obesity. WAT mass is composed primarily of mature adipocytes, which are generated through the proliferation and differentiation of adipocyte precursors (APs). Although the production of new adipocytes contributes to WAT growth in obesity, little is known about the cellular and molecular mechanisms underlying adipogenesis in vivo. Here, we show that high-fat diet feeding in mice rapidly and transiently induces proliferation of APs within WAT to produce new adipocytes. Importantly, the activation of adipogenesis is specific to the perigonadal visceral depot in male mice, consistent with the patterns of obesogenic WAT growth observed in humans. Furthermore, we find that in multiple models of obesity, the activation of APs is dependent on the phosphoinositide 3-kinase (PI3K)-AKT2 pathway; however, the development of WAT does not require AKT2. These data indicate that developmental and obesogenic adipogenesis are regulated through distinct molecular mechanisms.
Department of Cell Biology, Yale University, Yale University School of Medicine, 375 Congress Ave New Haven, Connecticut 06520, USA.
Elise
E
Jeffery
Section of Comparative Medicine, Yale University, Yale University School of Medicine, 375 Congress Ave New Haven, Connecticut 06520, USA.
Christopher D
CD
Church
Department of Molecular, Cell and Developmental Biology, Yale University, Yale University School of Medicine, 375 Congress Ave New Haven, Connecticut 06520, USA.
Brandon
B
Holtrup
Section of Comparative Medicine, Yale University, Yale University School of Medicine, 375 Congress Ave New Haven, Connecticut 06520, USA.
Laura
L
Colman
1] Section of Comparative Medicine, Yale University, Yale University School of Medicine, 375 Congress Ave New Haven, Connecticut 06520, USA [2] Department of Molecular, Cell and Developmental Biology, Yale University, Yale University School of Medicine, 375 Congress Ave New Haven, Connecticut 06520, USA [3] Yale Stem Cell Center, Yale University, Yale University School of Medicine, 375 Congress Ave New Haven, Connecticut 06520, USA.
Matthew S
MS
Rodeheffer
D052438:Adipocytes, White / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D052436:Adipose Tissue, White; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D059305:Diet, High-Fat; D004435:Eating; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D011897:Random Allocation; D013629:Tamoxifen / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D013629:Tamoxifen; D000077191:Wortmannin; C494922:Akt2 protein, mouse