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Novel Roles for Catestatin in Cardiac Metabolism and Physiology
Author(s) -
Schilling Jan,
Pasqua Teresa,
Avolio Ennio,
ZemljicHarpf Alice,
Headrick John,
Kassan Adam,
Bandyopadhyay Gautam,
Roth David,
Patel Hemal,
Mahata Sushil
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1025.12
Subject(s) - cardioprotection , medicine , endocrinology , glycogen , insulin , ischemia
More than 50 million people suffer from cardiometabolic syndrome in the US. Catestatin (CST), a peptide derived form chromogranin A, acts as an antihypertensive, cardioprotective, pro‐angiogenic, and insulin‐sensitizing peptide. The role of CST in cardioprotection and substrate utilization under normal and stressed conditions is not well understood. We hypothesized that CST is a key regulator of cardiac metabolism and stress adaptation. We investigated wild‐type (WT) and CST‐KO mice to evaluate cardiac function and metabolism. CST‐KO mice display hypertension, are hyperadrenergic, insulin resistant and show increased fasting plasma insulin and leptin. Fatty acid uptake and oxidation was higher in hearts of CST‐KO mice. Ultrastructural studies revealed more glycogen deposition, decreased sarcomere length, and altered mitochondria in CST‐KO mice. We have seen that in the hearts of CST‐KO mice, pAMPK as well as insulin‐stimulated phosphorylation of Akt, and GSK‐3β were decreased. High fat diet (HFD) did not uncover differences in glycogen synthesis, but less glycogen was stored in CST‐KO‐HFD hearts. Comparison of injuries after ischemia reperfusion and ischemic preconditioning showed that protection of hearts from CST‐KO mice was not possible. The same holds true after HFD with worse recovery for CST KO mice. Our studies characterize the crucial role of CST in cardiac physiology and metabolism and suggest CST as a therapeutic target for modulating cardiometabolic disease.