Although these observations suggest that the anti-obesity activity of GDF-15 may be related to its anti-inflammatory effect, it remains to be seen whether the anti-inflammatory effect of GDF-15 on WAT is direct and independent of weight (e.g., through macrophages or other immune cells) or the effect of GDF-15 on low-grade inflammation is only indirect through weight loss [15]. Here, GDF15 is linked to obesity due to melanocortin 4 receptor deficiency.