In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 119, No. suppl_1 ( 2016-07-22)
Abstract:
Impaired cardiac insulin signaling and high cardiac fatty acid oxidation rates are characteristics of diabetic cardiomyopathy. Potential roles for liver-derived metabolic factors in mediating cardiac energy homeostasis are underappreciated. Plasma levels of adropin, a liver secreted peptide, increase during feeding and decrease during fasting and diabetes. In skeletal muscle, adropin preferentially promotes glucose over fatty acid oxidation. We therefore determined what effect adropin has on cardiac energy metabolism, insulin signaling and cardiac efficiency. C57Bl/6 mice were fasted to accentuate the differences in adropin plasma levels between animals injected 3 times over 24 hr with either vehicle or adropin (450 nmol/kg i.p.). Despite fasting-induced predominance of fatty acid oxidation measured in isolated working hearts, insulin inhibition of fatty acid oxidation was re-established in adropin-treated mice (from 1022±143 to 517±56 nmol. g dry wt -1 . min -1 , p 〈 0.05) compared to vehicle-treated mice (from 757±104 to 818±103 nmol. g dry wt -1 . min -1 ). Adropin-treated mice hearts showed higher cardiac work over the course of perfusion (p 〈 0.05 vs. vehicle), which was accompanied by improved cardiac efficiency and enhanced phosphorylation of insulin signaling enzymes (tyrosine-IRS-1, AS160, p 〈 0.05). Acute addition of adropin (2nM) to isolated working hearts from non-fasting mice showed a robust stimulation of glucose oxidation compared to vehicle-treated hearts (3025±401 vs 1708±292 nmol. g dry wt -1 . min -1 , p 〈 0.05, respectively) with a corresponding inhibition of palmitate oxidation (325±61 vs 731±160 nmol. g dry wt -1 . min -1 , p 〈 0.05, respectively), even in the presence of insulin. Acute adropin addition to hearts also increased IRS-1 tyrosine-phosphorylation as well as Akt, and GSK3β phosphorylation (p 〈 0.05), suggesting acute receptor- and/or post-translational modification-mediated mechanisms. These results suggest adropin as a putative candidate for the treatment of diabetic cardiomyopathy.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/res.119.suppl_1.282
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2016
detail.hit.zdb_id:
1467838-X
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