Sundarrajan Lakshminarasimhan, Rajeswari Jithine Jayakumar, Weber Lynn P, Unniappan Suraj
Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B4, Canada.
Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B4, Canada.
Comp Biochem Physiol A Mol Integr Physiol. 2021 Sep;259:111016. doi: 10.1016/j.cbpa.2021.111016. Epub 2021 Jun 11.
Irisin is a 23 kDa myokine encoded in its precursor, fibronectin type III domain containing 5 (FNDC5). The exercise-induced increase in the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α) promotes FNDC5 mRNA, followed by the proteolytic cleavage of FNDC5 to release irisin from the skeletal or cardiac muscle into the blood. Irisin is abundantly expressed in skeletal and cardiac muscle and plays an important role in feeding, modulates appetite regulatory peptides, and regulates cardiovascular functions in zebrafish. In order to determine the potential mechanisms of acute irisin effects, in this research, we explored whether adrenergic or muscarinic pathways mediate the cardiovascular effects of irisin. Propranolol (100 ng/g B·W) alone modulated cardiac functions, and when injected in combination with irisin (0.1 ng/g B·W) attenuated the effects of irisin in regulating cardiovascular functions in zebrafish at 15 min post-injection. Atropine (100 ng/g B·W) modulated cardiovascular physiology in the absence of irisin, while it was ineffective in influencing irisin-induced effects on cardiovascular functions in zebrafish. At 1 h post-injection, irisin downregulated PGC-1 alpha mRNA, myostatin-a and myostatin-b mRNA expression in zebrafish heart and skeletal muscle. Propranolol alone had no effect on the expression of these mRNAs in zebrafish and did not alter the irisin-induced changes in expression. At 1 h post-injection, irisin siRNA downregulated PGC-1 alpha, troponin C and troponin T2D mRNA expression, while upregulating myostatin a and b mRNA expression in zebrafish heart and skeletal muscle. Atropine alone had no effects on mRNA expression, and was unable to alter effects on mRNA expression of siRNA. Overall, this research identified a role for the sympathetic/beta-adrenergic pathway in regulating irisin effects on cardiovascular physiology and cardiac gene expression in zebrafish.
鸢尾素是一种23千道尔顿的肌动蛋白，由其前体含III型纤连蛋白结构域5（FNDC5）编码。运动诱导的过氧化物酶体增殖物激活受体γ共激活因子1α（PGC1-α）表达增加会促进FNDC5 mRNA的生成，随后FNDC5发生蛋白水解切割，将鸢尾素从骨骼肌或心肌释放到血液中。鸢尾素在骨骼肌和心肌中大量表达，在摄食过程中发挥重要作用，调节食欲调节肽，并调节斑马鱼的心血管功能。为了确定鸢尾素急性作用的潜在机制，在本研究中，我们探讨了肾上腺素能或毒蕈碱能途径是否介导鸢尾素对心血管的影响。单独使用普萘洛尔（100纳克/克体重）可调节心脏功能，与鸢尾素（0.1纳克/克体重）联合注射时，在注射后15分钟可减弱鸢尾素对斑马鱼心血管功能的调节作用。阿托品（100纳克/克体重）在无鸢尾素时可调节心血管生理，但对鸢尾素诱导的斑马鱼心血管功能影响无效。注射后1小时，鸢尾素下调斑马鱼心脏和骨骼肌中PGC-1α mRNA、肌肉生长抑制素-a和肌肉生长抑制素-b mRNA的表达。单独使用普萘洛尔对斑马鱼中这些mRNA的表达没有影响，也没有改变鸢尾素诱导的表达变化。注射后1小时，鸢尾素siRNA下调斑马鱼心脏和骨骼肌中PGC-1α、肌钙蛋白C和肌钙蛋白T2D mRNA的表达，同时上调肌肉生长抑制素a和b mRNA的表达。单独使用阿托品对mRNA表达没有影响，也无法改变siRNA对mRNA表达的影响。总体而言，本研究确定了交感神经/β-肾上腺素能途径在调节鸢尾素对斑马鱼心血管生理和心脏基因表达的影响中的作用。
