Obesity and type-2-diabetes in humans, as well as high-fat feeding in mice, have been shown to exhibit increased expression of Trib3 in skeletal muscle [48, 49], while Trib3 knockout mice were protected from glucose-induced IR, suggesting TRIB3 to be a critical response factor in nutrient excess [33, 47, 50]. Here, TRIB3 is linked to obesity due to melanocortin 4 receptor deficiency.