CPA3 and Insulin resistance: To further substantiate the observations that mast cell Tph1 promotes obesity and insulin resistance without the potential confounding metabolic effects of the KitW-sh/W-sh mutation28, we removed Tph1 in mast cells by crossing Tph1 floxed mice with mice expressing Cre recombinase linked to carboxypeptidase 3 promoter (Cpa3-Cre) to generate Tph1 mast cell null mice (Tph1 MCKO) (Fig. 3a) and confirmed deletion in intraperitoneal mast cells (Supplementary Fig. 2i).