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Soon after the discovery of the muscle-derived factor irisin, a great controversy arose in the literature regarding certain inconsistencies in the regulation of the fibronectin type III domain containing 5 protein ( FNDC5/irisin) after exercise, as well as the unpredicted association of circulating irisin levels with parameters of adiposity in humans. Due to these questionable findings, doubts as to the identity of the soluble portion of FNDC5 as well as the real role of irisin and its possible therapeutic applications in the treatment of obesity and diabetes have proliferated. We recently postulated that FNDC5/irisin is an adipokine expressed and secreted by white adipose tissue in rats and humans. Its circulating concentration correlates with adiposity in humans among independent cohorts of patients. Further analysis, focused on obesity-related metabolic disorders, has shown that irisin could play a role in promoting insulin resistance or act as an adaptive response to counteract disturbances in glucose and lipid homoeostasis in obesity. Overall, this leads us to raise the question whether the new factor, increased in circulation of obese patients, is really irisin-reflecting fat mass or it is an artefact. Therefore, the current review is focused on the potential participation of adipose tissue in irisin circulating levels, and the role of irisin in metabolic pathologies associated with obesity in an attempt to clarify the controversy generated by these recently published reports. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to determine if genetic variation in the pain-modulating gene DREAM and its pathway genes influence susceptibility to reporting musculoskeletal pain in the population. Methods Pairwise tag single nucleotide polymorphisms ( SNPs) in DREAM, PDYN and OPRK1 were genotyped in a UK population-based discovery cohort in whom pain was assessed using blank body manikins at three time points. Depression and anxiety symptoms were assessed at the first time point. Zero-inflated negative binomial regression was used to test for association between SNPs and the maximum number of pain sites reported (0-29) across the three time points. Significantly associated SNPs ( p < 0.05) were subsequently genotyped for validation in a cohort of European men with pain assessed at two time points. Results Thirty-five SNPs were genotyped in 1055 subjects, of whom 83% reported pain, in the discovery cohort. SNPs in each gene were associated with the maximum number of pain sites reported, were independent of symptoms of anxiety and depression and had a significant cumulative effect ( p = 7.0 × 10−5). Significantly associated SNPs were successfully genotyped in 1733 men, 76% of whom reported pain, in the validation cohort, but did not show significant association with the number of pain sites. Conclusions Genetic variation in the DREAM pathway genes was associated with the extent of pain reporting in a population-based cohort. These findings were not replicated in a single independent cohort; however, given the potential of this pathway as a therapeutic target, further investigation in additional cohorts is warranted. [ABSTRACT FROM AUTHOR]