title: Loss of white adipose hyperplastic potential is associated with enhanced susceptibility to insulin resistance.
abstract: Fat mass expansion occurs by adipocyte hypertrophy or recruitment of differentiating adipocyte progenitors, the relative balance of which may impact systemic metabolism. We measured adipogenesis in murine subcutaneous (sWAT) and visceral white adipose tissue (vWAT) using stable isotope methodology and then modeled adipocyte turnover. Birth and death rates were similar within depots; however, turnover was higher in vWAT relative to sWAT. In juvenile mice, obesity increased adipogenesis, but in adults, this was only seen in vWAT after prolonged high-fat feeding. Statistical modeling suggests differentiation of adipocyte progenitors without an accompanying self-renewing division step may partially explain the age-dependent decline in hyperplastic potential. Additional metabolic interrogation of obese mice demonstrated an association between adipocyte turnover and insulin sensitivity. These data therefore identify adipocyte hypertrophy as the dominant mechanism of adult fat mass expansion and support the paradoxical concept that metabolic disease ensues due to a failure of adipose tissue plasticity.
authors.affiliation: Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Soo M
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Lun
authors.affiliation: National Resource for Imaging Mass Spectroscopy, Brigham and Women's Hospital, Cambridge, MA 02138, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
authors.forename: Samuel E
authors.initials: SE
authors.lastname: Senyo
authors.affiliation: Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA; National Resource for Imaging Mass Spectroscopy, Brigham and Women's Hospital, Cambridge, MA 02138, USA; Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Christelle
authors.initials: C
authors.lastname: Guillermier
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Parth
authors.initials: P
authors.lastname: Patwari
authors.affiliation: Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: msteinhauser@partners.org.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Steinhauser
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis / Q000502:physiology; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015233:Models, Statistical