Permanent activation of HMGA2 in lipomas mimics its temporal physiological activation linked to the gain of adipose tissue

Obesity (Silver Spring). 2014 Jan;22(1):141-50. doi: 10.1002/oby.20137. Epub 2013 Sep 17.

Abstract

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 p14(Arf) 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 up-regulate 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.

MeSH terms

  • Adipogenesis / genetics
  • Adipogenesis / physiology
  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Disease Models, Animal
  • Dogs
  • Female
  • Fibroblast Growth Factor 1 / pharmacology
  • Gene Rearrangement
  • HMGA2 Protein / genetics
  • HMGA2 Protein / metabolism*
  • Humans
  • Lipoma / metabolism*
  • Male
  • Overweight / genetics
  • Overweight / metabolism
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Stem Cells / metabolism
  • Subcutaneous Fat, Abdominal / cytology*
  • Tumor Suppressor Protein p14ARF / genetics
  • Tumor Suppressor Protein p14ARF / metabolism
  • Up-Regulation

Substances

  • HMGA2 Protein
  • PPAR gamma
  • RNA, Messenger
  • Tumor Suppressor Protein p14ARF
  • Fibroblast Growth Factor 1