Data presented in this paper indicate that loss of TG2 indeed enhances obesity-related pathologies such as adipose tissue inflammation, adipocyte death, hepatic steatosis and insulin resistance in mice exposed to either HSD or to HFD, and all this is a result of the loss of TG2 from bone marrow-derived cells. This evidence concerns the gene TGM2 and obesity due to melanocortin 4 receptor deficiency.