A population of T cells mediates weight loss via an FGF21-dependent mechanism, according to new data. In obese mice, in which invariant natural killer T (iNKT) cells were activated with α-galactosylceramide, weight loss was accompanied by increases in body temperature, fatty acid oxidation, thermogenic browning of white adipose tissue and serum levels of FGF21. Weight loss following activation of iNKT cells was markedly reduced in similarly treated FGF21-deficient mice, confirming the involvement of FGF21. As the glucagon-like peptide 1 agonist liraglutide also activates iNKT cells to induce weight loss, targeting the iNKT cell–FGF21 axis could be a promising approach to regulate weight.