Vliora Maria, Grillo Elisabetta, Corsini Michela, Ravelli Cosetta, Nintou Eleni, Karligiotou Eleni, Flouris Andreas D, Mitola Stefania
FAME Laboratory, Department of Exercise Science, University of Thessaly, Trikala, Greece; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Biochim Biophys Acta Gen Subj. 2022 Apr;1866(4):130085. doi: 10.1016/j.bbagen.2022.130085. Epub 2022 Jan 10.
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.
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.
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.
Our data supports the role of irisin in the induction of non-shivering thermogenesis, the regulation of energy expenditure and lipolysis in adipocytes.
Irisin may be an attractive therapeutic target in the treatment of obesity and related metabolic disorders.
脂肪组织在代谢综合征的发生和发展中起关键作用,代谢综合征及其并发症是21世纪的一种流行病。鸢尾素是一种主要由骨骼肌分泌的脂肪肌动蛋白,其作用靶点包括脂肪组织等。在棕色脂肪组织中,它上调解偶联蛋白-1(UCP1),该蛋白负责线粒体非颤抖性产热。
在此,我们通过线粒体通量分析来分析鸢尾素对3T3-L1来源的脂肪细胞代谢活性的影响。我们还通过蛋白质免疫印迹法评估鸢尾素对细胞内信号传导的影响。最后,通过逆转录定量聚合酶链反应检测ucp1和脂解基因的基因表达。
鸢尾素通过调节PI3K-AKT途径以时间依赖性方式影响线粒体呼吸和脂解。鸢尾素还诱导UCP1的表达并调节NF-κB、CREB和ERK途径。
我们的数据支持鸢尾素在诱导非颤抖性产热、调节脂肪细胞能量消耗和脂解中的作用。
鸢尾素可能是治疗肥胖症及相关代谢紊乱的一个有吸引力的治疗靶点。