There is a clear link between overweight, gain of white adipose tissue, and diabetes type 2 (T2D). The molecular mechanism of the gain of adipose tissue is linked with the expression of high mobility group protein AT-hook 2 (HMGA2), and recent studies revealed an association with a SNP near HMGA2. In this study, we investigated the gene expression of HMGA2, p14Arf , CDKN1A, and BAX in human abdominal subcutaneous white adipose tissue from 157 patients. We found a significant higher HMGA2 expression in obese individuals than in non-obese patients. Furthermore, the HMGA2 expression in white adipose tissue in patient with type 2 diabetes was significantly higher than in nondiabetic patients. There is an association between the DNA-binding nonhistone protein HMGA2 and the risk of developing T2D that remains mechanistically unexplained so far. Likewise, p14Arf , an inducer of cellular senescence, has been associated with the occurrence of T2D. The data of the present study provide evidence that both proteins act within the same network to drive proliferation of adipose tissue stem and precursor cells, senescence, and increased risk of T2D, respectively.
Objective: In this study the activation of HMGA2 and overexpression by FGF1-driven stimulation of adipose tissue derived stem cells (ADSCs) in adipose tissue tumors were analyzed. In addition, the expression of HMGA2 and PPAR-gamma mRNA were quantified in canine subcutaneous abdominal adipose tissue from normal and overweight purebred dogs. Design and Methods: ADSCs and adipose tissue explants stimulated with FGF1 followed by gene expression analyses of HMGA2 and p14Arf using Western-blot and qRT-PCR. Furthermore, canine subcutaneous white adipose tissue (WAT) were analyzed by qRT-PCR for their expression of HMGA2 and PPAR-gamma.Results: ADSCs and adipose tissue explants are able to execute a HMGA2 response upon FGF1 stimulation. FGF1 enhances proliferation of ADSCs by a HMGA2-dependent mechanism. In lipomas increase of HMGA2 is accompanied by increased expression of p14 Arf . Furthermore, a significantly elevated level of HMGA2 in overweight dogs and a negative correlation between the expression of HMGA2 and PPAR-gamma in subcutaneous cWAT were noted. Conclusions: These results suggest that WAT contains cells that as essential part of adipogenesis upregulate HMGA2 resulting from growth factor stimulation. In subgroups of lipoma, constitutive activation of HMGA2 due to rearrangements replaces the temporal response triggered by growth factors.
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