Uncoupling protein 2 (UCP2) is often upregulated in cancer cells. The UCP2 upregulation is positively correlated with enhanced proliferation, tumorigenesis, and metabolic alterations, thus suggesting that UCP2 upregulation could play a key role in sensing metabolic changes to promote tumorigenesis. To determine the global metabolic impact of UCP2 upregulation, we used 13C6 glucose as a source molecule to ‘trace’ the metabolic fate of carbon atoms derived from glucose. UCP2 overexpression in skin epidermal cells enhanced the incorporation of 13C-label to pyruvate, TCA cycle intermediates, nucleotides, and amino acids, suggesting that UCP2 upregulation reprograms cellular metabolism towards macromolecule synthesis. To the best of our knowledge, this is the first study to bring to light the overall metabolic differences caused by UCP2 upregulation.