A landmark study by Gregory R. Steinberg’s team at McMaster University, published in Nature, demonstrated that the GDF15-GFRAL pathway increases skeletal muscle calcium futile cycling to simultaneously suppress appetite and maintain energy expenditure during caloric restriction, providing a novel solution to overcome the challenge of “weight rebound” in obesity management [27]. This evidence concerns the gene GDF15 and obesity due to melanocortin 4 receptor deficiency.