Mice with EpoR restricted to erythroid tissue survive to adulthood with no gross morphological abnormalities, providing evidence that EpoR is required only for red blood cell production, although these mice exhibit increased susceptibility to stress response such as pulmonary hypertension, skeletal muscle injury, and inflammation in diet induced obesity, and these mice become obese, glucose intolerant and insulin resistant. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.