INS and obesity due to melanocortin 4 receptor deficiency: By administering anti-HMGB1antibody to C57Bl/6 mice, Montes et al. (Montes et al. 2015) previously reported that anti-HMGB1 treatment reduced weight gain in mice fed a high (60%)-fat diet from the 2nd week and thus HMGB1 was inferred to play a crucial role in weight gain at the early stage of obesity, though they did not observe differences in glucose, insulin tolerance and adipose tissue inflammation between HMGB1 neutralizing and control groups.