PTHLH and Cachexia: Prior to the publication of this paper, Spiegelman's group discovered that PTH-related protein (PTHrP), a tumor-derived protein that causes hypercalcemia of malignancy, directly acts on white adipocytes to induce a phenotypic switch to brown adipocytes (a phenomenon termed adipose tissue browning) and thereby triggers energy wasting in fat tissues, leading to cachexia [28].