Interestingly, biopsies from well-characterized patients with defined obesity, type 2 diabetes (T2D) and MASLD status, along with male mouse models of obesity and MASLD, revealed that adipose tissue is the primary source of GDF15 during the early stages of obesity and T2D, where GDF15 expression is increased through the accumulation of macrophages, and inactivation of Gdf15 in macrophages exacerbates obesity in mice [162]. This evidence concerns the gene GDF15 and obesity due to melanocortin 4 receptor deficiency.