SFEBES2012 Poster Presentations Obesity, diabetes, metabolism and cardiovascular (73 abstracts)
Background: The detrimental effect of excessive obesity on insulin resistance has been well established. The expansion of adipose tissue is closely dependent on two processes: adipogenesis and angiogenesis and the Wnt signalling pathway has been reported to affect both. In adipose tissue the Wnt signalling pathway functions in a converse manner: increasing commitment of mesenchymal stem cells to preadipocytes and inhibiting differentiation of preadipocytes to mature adipocytes by decreasing expression of CEBPα and PPARγ. One of the antagonists of the canonical Wnt signalling pathway is secreted frizzled-related protein 2 (sFRP2 protein) however, recent studies have identified sFRP2 as a novel factor stimulating angiogenesis via a non-canonical, calcineurin/NFAT signalling pathway Expression of sFRP2 and Wnt receptors, Fzd1 and Fzd2, mRNA has been reported in preadipocytes and Wnt signalling is also known to be involved in pancreatic islet function, insulin production and secretion. Therefore we hypothesised that sFRP2 secreted from adipose tissue could provide a link between obesity and diabetes through a deleterious action on β cells/insulin secretion.
Results: Human omental and subcutaneous adipose tissues expressed high levels of sFRP2 mRNA. sFRP2 mRNA was present in mouse gonadal and subcutaneous fats but absent in mouse liver, pancreas as well as pancreatic α- and β-cell lines (TC1.9 and MIN6 cells, respectively). All mouse tissues and cells studied were positive for Wnt signalling receptors Fzd1 and Fzd2. When proliferating mouse pancreatic α- and β-cells were treated with recombinant mouse sFRP2 protein (10 ng to 200 ng/ml) for 4 days, we observed a dose dependent decrease in proliferation rates of β-cells (10 ng/ml: 96%, 100 ng/ml: 84%, 200 ng/ml: 72% vs 100% control, P<0.01) but not α-cells or human preadipocyte cell line, Chub7.
Conclusion: We postulate that secreted sFRP2 from expanding adipose tissue could have a harmful effect on pancreatic β cell function and contribute to the pathogenesis of insulin resistance in human obesity.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.