Although
mast cell functions have classically been related to
allergic responses, recent studies indicate that these cells contribute to other common diseases such as
multiple sclerosis,
rheumatoid arthritis,
atherosclerosis,
aortic aneurysm and cancer. This study presents evidence that
mast cells also contribute to diet-induced
obesity and
diabetes. For example, white
adipose tissue (WAT) from
obese humans and
mice contain more
mast cells than WAT from their lean counterparts. Furthermore, in the context of
mice on a Western diet,
genetically induced deficiency of
mast cells, or their
pharmacological stabilization, reduces
body weight gain and levels of
inflammatory cytokines,
chemokines and
proteases in serum and WAT, in concert with improved
glucose homeostasis and energy expenditure. Mechanistic studies reveal that
mast cells contribute to WAT and
muscle angiogenesis and associated cell
apoptosis and
cathepsin activity. Adoptive transfer experiments of cytokine-deficient
mast cells show that these cells, by producing interleukin-6 (IL-6) and
interferon-gamma (
IFN-gamma), contribute to
mouse adipose tissue cysteine protease cathepsin expression,
apoptosis and
angiogenesis, thereby promoting diet-induced
obesity and
glucose intolerance. Our results showing reduced
obesity and
diabetes in
mice treated with clinically available mast cell-stabilizing agents suggest the potential of developing new therapies for these common human
metabolic disorders.
