Maiadah Alfares
University of Bristol, UK
Title: A novel role for insulin like growth factor II (IGF-II) in adipocyte regulation: Site-specific actions due to differences in insulin receptor distribution
Biography
Biography: Maiadah Alfares
Abstract
IGF-II levels in the circulation are maintained at high levels throughout life and IGF-II has been strongly linked to obesity in genetic studies but its metabolic role is still far from understood.We aim to investigate the role of IGF-II as a regulator of adipocytes and its specific effects on visceral adipocytes in relation to the differential distribution of insulin receptors between visceral and subcutaneous fat depots and the possible metabolic consequences.Matched pairs of visceral and subcutaneous pre-adipocytes were collected from biopsies of normal children undergoing routine surgery for non-malignant, non-septic conditions. These cells were grown and differentiated into mature adipocytes using a unique adipocyte cell culture system developed in our laboratory.Tritiated thymidine incorporation Assay (TTI) was used to assess cell proliferation after dosing with IGF-II in different glycaemic conditions (5 & 25 mM). Oil red O staining, western blotting and reverse transcription polymerase chain reaction (RT-PCR) techniques were employed to assess levels of adipogenesis markers and levels of the insulin receptor and insulin receptor isoforms.We found that IGF-II could promote proliferation of primary preadipocytes from subcutaneous and visceral fat depots and this proliferative effect was more profound in subcutaneous preadipocytes in euglycemic (5mM) conditions. Furthermore, IGF-II promoted preadipocyte differentiation into adipocytes in subcutaneous preadipocytes but showed an inhibitory effect on visceral preadipocyte differentiation. Visceral adipocytes had a higher level of insulin receptors in comparison to subcutaneous preadipocytes and IGF-II caused a down regulation of insulin receptor mRNA expression that was more profound in visceral fat cells. In conclusion, IGF-II is a regulator of preadipocyte proliferation and this effect is altered by the concentration of glucose. IGF-II may have a protective role against visceral adiposity by reducing preadipocyte differentiation into mature adipocytes and by reducing insulin receptor expression.