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

• Published in: Cell metabolism Vol. 20; no. 6; pp. 1049 - 1058
• Main Authors: Kim, Soo M., Lun, Mingyue, Wang, Mei, Senyo, Samuel E., Guillermier, Christelle, Patwari, Parth, Steinhauser, Matthew L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02-12-2014
• Subjects: Adipocytes - cytology; Adipocytes - metabolism; Adipogenesis - physiology; Adipose Tissue, White - metabolism; Animals; Insulin Resistance - physiology; Male; Mice; Mice, Inbred C57BL; Models, Statistical
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2014.10.010

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.
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•Stable isotopes can be used to quantitatively track adipogenesis in vivo•Visceral fat is more plastic than subcutaneous fat•Fat cell hypertrophy is the dominant mechanism of fat mass expansion in the adult•Subcutaneous adipogenesis is associated with measures of insulin sensitivity
The role of new fat cell generation in obesity is unclear. Using stable isotope methodology, Kim et al. demonstrate age-dependent decline in adipogenesis. Obesity increased adipogenesis during postnatal development, but this plasticity disappeared in adulthood. A positive association between adipocyte turnover and metabolic health suggests that adipogenesis is an adaptive response.