FNDC5/irisin has been recently postulated as beneficial in the treatment of obesity and diabetes because it is induced in muscle by exercise, increasing energy expenditure. However, recent reports have shown that WAT also secretes irisin and that circulating irisin is elevated in obese subjects. The aim of this study was to evaluate irisin levels in conditions of extreme BMI and its correlation with basal metabolism and daily activity. The study involved 145 female patients, including 96 with extreme BMIs (30 anorexic (AN) and 66 obese (OB)) and 49 healthy normal weight (NW). The plasma irisin levels were significantly elevated in the OB patients compared with the AN and NW patients. Irisin also correlated positively with body weight, BMI, and fat mass. The OB patients exhibited the highest REE and higher daily physical activity compared with the AN patients but lower activity compared with the NW patients. The irisin levels were inversely correlated with daily physical activity and directly correlated with REE. Fat mass contributed to most of the variability of the irisin plasma levels independently of the other studied parameters. Conclusion. Irisin levels are influenced by energy expenditure independently of daily physical activity but fat mass is the main contributing factor. ; Journal Article; This work was supported by CIBERobn (CB06/03), INTRASALUD Project (no. PI10/02464), and PI13/01915, Instituto de Salud Carlos III (ISCIII) initiatives. The study was also supported by Fondo de Investigación Sanitaria-FIS (PI11/210) and AGAUR (2009SGR1554). Ana B. Crujeiras is funded by the ISCIII through a research contract “Sara Borrell” (C09/00365). María Pardo is a Miguel Servet Fellow (ISCIII/SERGAS). Ana B. Fagundo is funded by Ministerio de Ciencia e Innovación Subprograma through a research contract Juan de la Cierva (JCI-2011-09248). José C. Fernández-García is recipient of a “Rio Hortega” contract from “Instituto de Salud Carlos III,” Madrid, Spain (CM12/00059).