Nat. Metab. 2, 50–61 (2020)

A ketogenic diet (KD; 90% fat, <1% carbohydrate) induces the formation of ketone bodies and is linked to weight loss and reduced inflammation. In Nature Metabolism, Dixit and colleagues show that a 1-week-long KD (stKD) activates a subset of adipose-tissue-resident γδ T cells that support tissue repair and homeostasis, while a 2–3 months long KD (ltKD) depletes these cells and induces obesity and glucose intolerance. As indicated by single-cell and bulk RNA-seq in the epididymal fat, stKD increases a population of strictly tissue-resident γδ T cells; induces the expression of genes involved in fatty acid metabolism, mitochondrial oxidation, cell trafficking and adhesion; and reduces the expression of Nlrp3 and Il1b. ltKD induces obesity, depletes the γδ T cells in adipose tissue and increases the expression of the proinflammatory genes Tnf and Il1b. ltKD in Tcr–/– mice, which lack γδ T cells, results in increased weight gain and metabolic alterations compared to those in wild-type mice, indicating these cells are protective.