Differentiation of white and brown adipocytes from precursor cells is key to the understanding of insulin resistance and obesity. Calcitonin gene related peptide (CGRP), widely expressed in human tissues, appears to impact on fat cell differentiation and function. However, the mechanism of action in fat cell differentiation is currently unknown. CGRP alters in a depot-specific manner the mass of white adipose tissue (WAT). It is controlled by stimuli like a lipid-rich meal, but this effects appears only be present in obese, not in lean subjects. Most importantly, CGRP deficient mice are protected against diet-induced obesity. They exhibit increased insulin sensitivity in parallel with increased energy expenditure.

In the present project we will investigate the CGRP dependent differentiation from mesenchymal to mature fat cells and the interaction with known regulators of differentiation.

Our group has long-term experience in the molecular and functional characterisation of mesenchymal cells, murine preadipocytes and mature cells from different fat cell depots. Experimental protocols include the measurement of glucose transporters, glucose uptake, insulin sensitivity, oxygen consumption, mitochondrial biogenesis/function and the expression/secretion of adipokines. Results from the mouse model will be transferred to human primary adipocytes in collaboration with a close collaborator at the University of Warwick who developed the expertise to work on human adipocyte function/dysfunction during weight gain and disease, assessing the impact of adipokines, differentiation and metabolism.