IRS1 and obesity due to melanocortin 4 receptor deficiency: In the development of obesity, there is greater infiltration of immune cells in this tissue, particularly macrophages, which show increased expression of TLR4.90 Free fatty acids bind to TLR-4, activating JNK and IκB kinase (IKK).91 Because IRS-1 are target of both enzymes, this process affects tyrosine phosphorylation, resulting in reduced GLUT4 translocation.92