Loss of White Adipose Hyperplastic Potential Is Associated with Enhanced Susceptibility to Insulin Resistance

被引:163
作者
Kim, Soo M. [1 ]
Lun, Mingyue [1 ]
Wang, Mei [2 ]
Senyo, Samuel E. [3 ,4 ,5 ]
Guillermier, Christelle [1 ,2 ,4 ]
Patwari, Parth [4 ]
Steinhauser, Matthew L. [1 ,3 ,4 ,5 ]
机构
[1] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Natl Resource Imaging Mass Spect, Cambridge, MA 02138 USA
[3] Brigham & Womens Hosp, Div Cardiovasc Med, Dept Med, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Boston, MA 02115 USA
[5] Harvard Stem Cell Inst, Cambridge, MA 02138 USA
关键词
IMAGING MASS-SPECTROMETRY; IN-VIVO; STABLE-ISOTOPES; FAT; TISSUE; CELLS; OBESITY; PROLIFERATION; METABOLISM; MOUSE;
D O I
10.1016/j.cmet.2014.10.010
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1049 / 1058
页数:10
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