I n this issue of Archives of Endocrinology and Metabolism, two articles help to increase our knowledge about the connections between thyroid status and energy metabolism. Although the relation between thyroid disease with obesity and metabolic dysfunction has been well established for many decades, some of their linking mechanisms are surprisingly still poorly understood.In the first paper, a cross-sectional observational study, Ates and cols.(1) measured irisin levels of 37 patients with newly diagnosed hypothyroidism (and a mean TSH of 13.1 mIU/L) and 37 healthy volunteers.Irisin is a recently identified proliferator-activated receptor-gamma coactivator-1α (PGC-1α)-dependent myokine that drives browning of white fat via elevation of uncoupling protein-1 (UCP-1), leading to thermogenesis and metabolic improvement (2). It was demonstrated to be a cleavage product of the extracellular portion of type I membrane protein fibronectin type III domain containing 5 (FNDC5), that is released after physical activity. The isolation of irisin in 2012 led to a great rush in understanding its function and metabolic relevance, as it was initially considered one of the main drivers of the beneficial effects of exercise (2,3). However, its impact was weakened by further studies that questioned the metabolic relevance of irisin in humans since there is a substantial controversy whether humans are able to cleave the protein FNDC5 (4,5). This would happen due to humans have a truncated form of FNDC5 gene, and as a result, irisin levels be insignificant, and its detection in serum would be due to analytical interferences. Even though this theory is up to this time a matter of debate, many publications about irisin have arisen in the last years, both in animals and humans.Another disappointment about the potential role of irisin in metabolic improvement (and maybe as a potential therapeutic agent) was the observation that obese individuals and patients with metabolic syndrome have higher levels of irisin and that weight loss (regardless of whether through caloric restriction or bariatric surgery) leads to a decrease in irisin levels (6-8). Could this phenomenon be due to an "irisin resistance" analogous to insulin or leptin resistance or it could be due to a defense against metabolic impairment? These are questions still unanswered, and the first study in this journal issue points in the same controversial direction, demonstrating higher levels of irisin in hypothyroid patients (1). In the study, the mean BMI was not statistically different between groups (27.77 vs 26.11 kg/m 2 , in hypothyroid and control groups, respectively) and the main parameters associated with irisin levels were age, TSH and free T4 levels. On one hand, these results are in agreement with a study in a murine model of thyroid dysfunction, in which an upregulation of irisin levels in both hyper and hypothyroid rats, as well as a positive correlation between irisin and