Maria Vliora1, Elisabetta Grillo2, Michela Corsini2, Cosetta Ravelli2, Eleni Nintou3, Eleni Karligiotou3, Andreas D Flouris3, Stefania Mitola4. 1. FAME Laboratory, Department of Exercise Science, University of Thessaly, Trikala, Greece; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. Electronic address: mvliora@uth.gr. 2. Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. 3. FAME Laboratory, Department of Exercise Science, University of Thessaly, Trikala, Greece. 4. Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. Electronic address: stefania.mitola@unibs.it.
Abstract
BACKGROUND: Adipose tissue plays a pivotal role in the development and progression of the metabolic syndrome which along with its complications is an epidemic of the 21st century. Irisin is an adipo-myokine secreted mainly by skeletal muscle and targeting, among others, adipose tissue. In brown adipose tissue it upregulates uncoupling protein-1 (UCP1) which is responsible for mitochondrial non-shivering thermogenesis. METHODS: Here we analyzed the effects of irisin on the metabolic activity of 3T3-L1 derived adipocytes through a mitochondrial flux assay. We also assessed the effects of irisin on the intracellular signaling through Western Blot. Finally, the gene expression of ucp1 and lipolytic genes was examined through RT-qPCR. RESULTS: Irisin affects mitochondrial respiration and lipolysis in a time-dependent manner through the regulation of PI3K-AKT pathway. Irisin also induces the expression of UCP1 and the regulation of NF-κB, and CREB and ERK pathways. CONCLUSION: Our data supports the role of irisin in the induction of non-shivering thermogenesis, the regulation of energy expenditure and lipolysis in adipocytes. GENERAL SIGNIFICANCE: Irisin may be an attractive therapeutic target in the treatment of obesity and related metabolic disorders.
BACKGROUND: Adipose tissue plays a pivotal role in the development and progression of the metabolic syndrome which along with its complications is an epidemic of the 21st century. Irisin is an adipo-myokine secreted mainly by skeletal muscle and targeting, among others, adipose tissue. In brown adipose tissue it upregulates uncoupling protein-1 (UCP1) which is responsible for mitochondrial non-shivering thermogenesis. METHODS: Here we analyzed the effects of irisin on the metabolic activity of 3T3-L1 derived adipocytes through a mitochondrial flux assay. We also assessed the effects of irisin on the intracellular signaling through Western Blot. Finally, the gene expression of ucp1 and lipolytic genes was examined through RT-qPCR. RESULTS: Irisin affects mitochondrial respiration and lipolysis in a time-dependent manner through the regulation of PI3K-AKT pathway. Irisin also induces the expression of UCP1 and the regulation of NF-κB, and CREB and ERK pathways. CONCLUSION: Our data supports the role of irisin in the induction of non-shivering thermogenesis, the regulation of energy expenditure and lipolysis in adipocytes. GENERAL SIGNIFICANCE: Irisin may be an attractive therapeutic target in the treatment of obesity and related metabolic disorders.