In sfrp5-mutated mice model fed a high-calorie diet, Ouchi et al.18 observed severe glucose intolerance and hepatic steatosis via activation of the c-Jun N-terminal kinase signaling pathway, while Mori et al. reported obesity-resistance via enhanced mitochondrial activities.19 In human beings, plasma sfrp5 concentration in T2D patients was declined in most reports.14,15,17 including ours, except one elevated.16 We figured that disagreement probably resulted from subjects with different diabetic durations and hence different inflammatory stages. Here, SFRP5 is linked to obesity due to melanocortin 4 receptor deficiency.