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FNDC5/irisin is not only a myokine but also an adipokine.

ABSTRACT: Exercise provides clear beneficial effects for the prevention of numerous diseases. However, many of the molecular events responsible for the curative and protective role of exercise remain elusive. The recent discovery of FNDC5/irisin protein that is liberated by muscle tissue in response to exercise might be an important finding with regard to this unsolved mechanism. The most striking aspect of this myokine is its alleged capacity to drive brown-fat development of white fat and thermogenesis. However, the nature and secretion form of this new protein is controversial. The present study reveals that rat skeletal muscle secretes a 25 kDa form of FNDC5, while the 12 kDa/irisin theoretical peptide was not detected. More importantly, this study is the first to reveal that white adipose tissue (WAT) also secretes FNDC5; hence, it may also behave as an adipokine. Our data using rat adipose tissue explants secretomes proves that visceral adipose tissue (VAT), and especially subcutaneous adipose tissue (SAT), express and secrete FNDC5. We also show that short-term periods of endurance exercise training induced FNDC5 secretion by SAT and VAT. Moreover, we observed that WAT significantly reduced FNDC5 secretion in fasting animals. Interestingly, WAT of obese animals over-secreted this hormone, which might suggest a type of resistance. Because 72% of circulating FNDC5/irisin was previously attributed to muscle secretion, our findings suggest a muscle-adipose tissue crosstalk through a regulatory feedback mechanism.

SUBMITTER: Roca-Rivada A

PROVIDER: S-EPMC3623960 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAdipokines and the myokine irisin, involved in mechanisms associated with obesity and metabolic syndrome (MS), are understudied in the pediatric population.ObjectiveTo investigate the relationship between irisin, and leptin, resistin, adiponectin, adipsin, anthropometric and cardiovascular risk factors in Mexican children.MethodsA cross-sample of 126 Mexican children aged 6-12 years old were classified as normal weight (n = 46), obese (n = 40), and MS (n = 40) according to CDC's and Cook's age-modified criteria for obesity and MS. Anthropometric parameters and blood pressure were determined and percentiles calculated for age and gender. Irisin, leptin, adiponectin, adipsin, resistin, triglycerides, glucose, high-density lipoprotein cholesterol (HDL-c) levels, and physical activity were determined. Statistical tests for differences between groups, correlation, and multiple regression analyses were performed.ResultsIrisin plasma levels were significantly lower in the obese (6.08 [4.68-6.65]) and MS groups (6.46 [5.74-7.02]) compared with the normal-weight group (8.05 [7.24-8.94]) (p < 0.001). Irisin levels were not influenced by age or gender, but significant dispersion was observed in obese girls (95% CI median [2.29-6.30]). Leptin, resistin, and adipsin levels were significantly increased in the obese and MS groups. Lean-fat ratio was significantly higher in the NW group. Irisin correlated negatively with leptin (- 0.310), resistin (- 0.389), adipsin (- 0.362), BMI% (-0.472), WC% (- 0.453), BMI z-score (- 0.496), fat free mass (- 0.257), fat percentage (- 0.532), fat mass (- 0.515), triglycerides (- 0.291), the number of cardiometabolic risk factors (- 0.443) (p < 0.001); positively with lean-fat ratio (0.489) and HDL-c (0.328) (p < 0.001) and none with physical activity (p < 0.001). Following stepwise multiple linear regression analysis, the lean-fat ratio was the only determinant of irisin levels (B = 1.168, p < 0.001).ConclusionsLean-fat ratio, more than the absolute amount of muscle or fat mass, as well as potential myokine-adipokine cross-talk mechanisms may explain the lower irisin levels in children with obesity and MS, through blunted compensatory responses interfering with tissue-dependent irisin secretion, contributing to a continuous deleterious effect cycle.

Project description:Background: FNDC5 belongs to the family of proteins called fibronectin type III domain-containing which carry out a variety of functions. The expression of FNDC5 is associated with the occurrence and development of tumors. However, the role of FNDC5 in gastric cancer remains relatively unknown. Methods: In the research, the expression of FNDC5 and its value for the prognosis of gastric cancer patients were observed with the TCGA database and GEO datasets of gastric cancer patients. The role of FNDC5 in the regulation of gastric cancer cells proliferation, invasion, and migration was determined. WGCNA and Enrichment analysis was performed on genes co-expressed with FNDC5 to identify potential FNDC5-related signaling pathways. Meanwhile, the LASSO Cox regression analysis based on FNDC5-related genes develops a risk score to predict the survival of gastric cancer patients. Results: The expression of FNDC5 was decreased in gastric cancer tissues compared to normal gastric tissues. However, survival analysis indicated that lower FNDC5 mRNA levels were associated with better overall survival and disease-free survival in gastric cancer patients. Meanwhile, a significant negative correlation was found between FNDC5 and the abundance of CD4+ memory T cells in gastric cancer. In vitro overexpression of FNDC5 inhibits the migration and invasion of gastric cancer cells, without affecting proliferation. Finally, A two-gene risk score module based on FNDC5 co-expressed gene was built to predict the overall clinical ending of patients. Conclusion: FNDC5 is low expressed in gastric cancer and low FNDC5 predicts a better prognosis. The better prognosis of low FNDC5 expression may be attributed to the increased number of CD4+ memory activated T-cell infiltration in tumors, but the exact mechanism of the effect needs to be further explored. Overexpressing FNDC5 inhibits the invasion and migration of gastric cancer but does not affect proliferation. At last, we constructed a clinical risk score model composed of two FNDC5-related genes, and this model may help lay the foundation for further in-depth research on the individualized treatment of gastric cancer patients.

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FNDC5/irisin is not only a myokine but also an adipokine.

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