This ties into the observations that C3aR KO mice are transiently resistant to weight gain, protected from high-fat diet-induced metabolic dysfunction and have less macrophage infiltration into adipose tissue [26], while C3KO mice are leaner, resistant to diet-induced obesity, with greater energy expenditure [45], [46], [47] and mice with increased C3 activation leading to excess C3a/C3adesArg (as seen in CD55KO and IL6KO mice) have increased adiposity [48], [49]. Here, C3 is linked to obesity due to melanocortin 4 receptor deficiency.