Signalling pathways important in human adipose tissue growth and function

Adipose tissue is a dynamic tissue which can grow and regress throughout the lifetime of an individual. The aim of this study is to understand the factors important in the regulation of adipocyte growth and function. Using human subcutaneous preadipocytes, the effects of insulin, dexamethasone, T3, and IBMX, alone and in combination, on different aspects of differentiation were examined. All 4 inducers were required in combination to induce a high level of differentiation. The PPAR$\gamma$ activator, rosiglitazone in conjunction with the 4 inducers induced the highest level of adipocyte differentiation. Inhibiting p38 MAPK and p70$^{S6K}$ reduced lipid content and lipogenic activity in differentiated preadipocytes while inhibiting p42/44 MAPK and PBK had no effect. Inhibiting p38 MAPK, p70$^{S6K}$ , p42/44 MAPK and PBK reduced leptin secretion but had no effect on protein content. Insulin and T3 caused the rapid activation of p42/44 MAPK in preadipocytes and differentiated preadipocytes, but dexamethasone, cortisol, oestrogen and rosiglitazone had no effect. Adipocytes expressed several growth factors i.e. FGF-2, VEGF, and angiopoietins. For FGF and its receptor, expression varied through differentiation. Inhibiting VEGF binding on adipocytes had no effect but inhibiting FGFR signalling and blocking angiopoietin action prevented growth and differentiation suggesting autocrine functions