Abstract
Adipogenesis in adulthood replaces fat cells that turn over and can contribute to the development of obesity. However, the proliferative potential of adipocyte progenitors in vivo is unknown (Faust et al., 1976; Faust et al., 1977; Hirsch and Han, 1969; Johnson and Hirsch, 1972). We addressed this by injecting labeled wild-type embryonic stem cells into blastocysts derived from lipodystrophic A-ZIP transgenic mice, which have a genetic block in adipogenesis. In the resulting chimeric animals, wild-type ES cells are the only source of mature adipocytes. We found that when chimeric animals were fed a high-fat-diet, animals with low levels of chimerism showed a significantly lower adipose tissue mass than animals with high levels of chimerism. The difference in adipose tissue mass was attributed to variability in the amount of subcutaneous adipose tissue as the amount of visceral fat was independent of the level of chimerism. Our findings thus suggest that proliferative potential of adipocyte precursors is limited and can restrain the development of obesity.
Highlights
Obesity is associated with a set of metabolic abnormalities, collectively known as the metabolic syndrome, which includes insulin resistance and diabetes, dyslipidemia, hypertension and an increased risk of cardiac disease (Grundy, 2004)
Wild-type:AZIP-chimeras were generated by injecting CAG-hTubYFP mouse B6-Tyrc ES-cells (EScells hereafter) into 3.5 day blastocysts generated by breeding wild-type (WT) FVB females to AZIP (FVB) transgenic males (Figure 1A). (Note, FVB mice do not become as obese as C57Bl/6J mice when fed a high fat diet so in subsequent experiments we studied B6 WT:AZIP chimeras, see below)
The extent of chimerism was quantified in a manner similar that used in a prior publication by calculating the ratio between the amount YFP-DNA and that of control genes, FABP4 or RPL23, which are expressed in all cells (Stanger et al, 2007)
Summary
Obesity is associated with a set of metabolic abnormalities, collectively known as the metabolic syndrome, which includes insulin resistance and diabetes, dyslipidemia, hypertension and an increased risk of cardiac disease (Grundy, 2004) These same abnormalities develop in lipodystrophy, a condition resulting from a reduced adipose tissue mass. The fact that both increased and decreased adipose tissue mass can cause metabolic disease has suggested that when the storage capacity of adipose tissue is exceeded, the result is ‘lipid overflow’, the deposition of excess lipid in peripheral tissues, leading to lipotoxicity, insulin resistance, and metabolic disease (Huang-Doran et al, 2010) This hypothesis suggests that the mechanisms that control adipose tissue development and the total amount (mass) of adipose tissue in vivo will be important for the pathogenesis of metabolic disease. Reduced leptin signaling leads to obesity in ob mice that lack leptin, and in animals fed a high fat diet (HFD) which causes leptin resistance (Friedman and Halaas, 1998)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
