The ongoing apoptosis in the AT, due to increases in fat mass, and consequent hypoxia, induces the release of “self” antigens, including cell-free DNA, and the release of class switched IgG antibodies which form immune complexes with “self” antigens, which in turn activate complement (C1q/C1qR/C3/C3a) and Fc receptors on immune cells, leading to enhanced local inflammation, remodeling of the AT, impairment of adipocyte function and of nutrient metabolism, and exacerbation of obesity-associated conditions. This evidence concerns the gene C3 and obesity due to melanocortin 4 receptor deficiency.