Effect of FGF21 on short-term white adipocyte adiponectin secretion

Abstract: Reduced levels of white adipocyte hormone adiponectin have been observed in obese individuals with type 2 diabetes (T2D). Higher adiponectin levels are monotonically associated with a lower risk of T2D and hence increasing circulating adiponectin levels is of great interest in diabetic research. A novel compound, called fibroblast growth factor 21 (FGF21), is showing great potential in treatment of obesity and T2D. In animal models with obesity and T2D FGF21 increases glucose uptake, improves lipid homeostasis, decreases fat mass and increases circulating adiponectin levels. In this study, theaim is to explore the acute effect of FGF21 on white adipocyte adiponectin secretion. Adiponectinsecretion experiments were performed on primary murine adipocytes incubated with FGF21 for 30minutes and adiponectin levels were measured with ELISA and normalised to total protein content.To study the signalling pathway of FGF21, a separate batch of murine adipocytes were pretreated with an Epac and PI3K inhibitor prior to addition of FGF21. Results from this thesis show that FGF21potently stimulates short-term adiponectin release via PI3K-dependent pathways with no effect on adiponectin synthesis.