Postgraduate research opportunities Role of mast cells in the development of obesity and diabetes

Obesity is a major health problem, being linked especially to the development of type 2 diabetes but also to cardiovascular disease and certain cancers. Current treatments are only moderately effective and a better understanding of the underlying pathophysiology of obesity is required. Cytokines, especially TNFα and IL-1, have been strongly implicated in the insulin resistance associated with obesity1. Recently, an important role for mast cells, a major source of these cytokines, was suggested by the reduced weight gain, reduced fat accumulation and improved glucose tolerance in mice lacking mast cells (KitW-sh/W-sh) placed on a western diet, which produced marked obesity in wild-type (WT) animals. A similar reduction in the development of obesity was produced by the mast-cell stabilising drugs disodium cromoglycate or ketotifen in WT mice fed a western diet. To further test the hypothesis that mast cells contribute to the development of obesity, the present study will examine the effect of mast cell stabilisation using disodium cromoglycate or mast cell depletion using compound 48/80 on the development of obesity in genetically obese mice (ob/ob).

Ob/ob mice will either receive 0.9% sodium chloride, daily injections of disodium cromoglycate or 48/80. Body weight and food intake will be measured daily for 12 weeks. At the end of 12 weeks the animals will be killed and a blood sample obtained for determination of blood glucose (Glucometer) and plasma insulin. The visceral adipose tissue will be dissected and weighed and samples of adipose tissue prepared for histology and for determination of TNFα and IL-1β. Tissue samples will be stained for mast cells and the diameters of adipocytes will be measured.  Additional studies will explore the development of obesity and diabetes in mast cell deficient

Techniques used

• Histology
• ELISA
• tissue culture
• flow cytometry
• in vivo biology

This project is also suitable for PhD Plus.

Further information

McKittrick CM, Lawrence CE, Carswell HV.  Mast cells promote blood brain barrier breakdown and neutrophil infiltration in a mouse model of focal cerebral ischemia.  J Cereb Blood Flow Metab. 2015 35:638-47

Wu J, Grassia G, Cambrook H, Ialenti A, MacRitchie N, Carberry J, Wadsworth RM, Lawrence C, Kennedy S, Maffia P.  Perivascular mast cells regulate vein graft neointimal formation and remodeling.  Peer J. 2015 Aug 18;3:e1192

Saunders KA1, Raine T, Cooke A, Lawrence CE.  Inhibition of autoimmune type 1 diabetes by gastrointestinal helminth infection. Infect Immun. 2007 75:397-407