Tissue specific TLR4 effects have been studied in the past and confirmed observation from global deletions, e.g. myeloid-specific (as well as global) TLR4-deficiency improves insulin sensitivity and inhibits obesity-induced tissue inflammation in HFD and lipid infusion models7,11,22,63,64. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.