BAT thermogenesis from uncoupling protein 1–mediated mitochondrial respiration likely contributes only a small fraction (i.e., less than 3%) of whole-body, cold-induced thermogenesis in humans. Skeletal muscle shivering and nonshivering thermogenesis drive most of the whole-body thermogenic response to cold. Glycerolipid and nonesterified fatty acid (GL/NEFA) substrate cycling activated in both WAT and BAT leads to systemic NEFA mobilization, likely driving NEFA reesterification in other organs (termed inter-organ GL/NEFA cycling) and also contributing to systemic energy expenditure.