PUBLICATION

The sympathetic/beta-adrenergic pathway mediates irisin regulation of cardiac functions in zebrafish

Authors
Sundarrajan, L., Rajeswari, J.J., Weber, L.P., Unniappan, S.
ID
ZDB-PUB-210616-24
Date
2021
Source
Comparative biochemistry and physiology. Part A, Molecular & integrative physiology   259: 111016 (Journal)
Registered Authors
Weber, Lynn
Keywords
Adrenergic pathway, Beta-blockers, Cardiovascular, Heart, Irisin, Zebrafish
MeSH Terms
  • Adrenergic beta-Antagonists/pharmacology
  • Animals
  • Atropine/pharmacology
  • Cardiovascular Physiological Phenomena
  • Cardiovascular System/drug effects
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Heart
  • Male
  • Muscle, Skeletal/metabolism
  • Myostatin/metabolism
  • Peptides
  • Propranolol/pharmacology
  • RNA, Messenger/metabolism
  • Transcription Factors/metabolism
  • Zebrafish/genetics*
  • Zebrafish Proteins/biosynthesis*
PubMed
34126232 Full text @ Comp. Biochem. Physiol. A Mol. Integr. Physiol.
Abstract
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 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 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 myostatins 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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping