In mice, beige adipose cells emerge from subcutaneous white adipose tissue in response to stimuli such as cold or β-adrenergic agonists, but their physiological role has not been fully elucidated. To explore this question, Bruce Spiegelman and colleagues generated mice in which the function of beige fat cells was selectively impaired by conditional deletion of a key transcriptional regulator, Prdm16, from adipocytes (Cell 156, 304–316, 2014). When fed normal chow, these mice showed no differences in food intake, activity or oxygen consumption. However, when challenged with a high-fat diet, they developed severe insulin resistance and obesity, accompanied by hepatic steatosis and a substantial increase in subcutaneous fat mass. Notably, the subcutaneous adipose tissue from these mice exhibited a gene expression profile resembling that of visceral fat, with reduced expression of thermogenic genes such as Ucp1 and elevated expression of proinflammatory genes. Together, these findings indicate that the Prdm16-dependent thermogenic program of beige adipose cells helps protect mice from adverse metabolic changes in response to a high-fat diet, and they provide further insights into the relationship between body fat distribution and disease risk.