Adropin regulates cardiac energy metabolism and improves cardiac function and efficiency

能量代谢 心功能曲线 功能(生物学) 心脏病学 内科学 环境科学 医学 生物 细胞生物学 心力衰竭
作者
Tariq Altamimi,Su Gao,Qutuba G. Karwi,Arata Fukushima,Sawan Kumar Rawat,Cory S. Wagg,Liyan Zhang,Gary D. Lopaschuk
出处
期刊:Metabolism-clinical and Experimental [Elsevier]
卷期号:98: 37-48 被引量:56
标识
DOI:10.1016/j.metabol.2019.06.005
摘要

Background Impaired cardiac insulin signalling and high cardiac fatty acid oxidation rates are characteristics of conditions of insulin resistance and diabetic cardiomyopathies. The potential role of liver-derived peptides such as adropin in mediating these changes in cardiac energy metabolism is unclear, despite the fact that in skeletal muscle adropin can preferentially promote glucose metabolism and improve insulin sensitivity. Objectives To determine the influence of adropin on cardiac energy metabolism, insulin signalling and cardiac efficiency. Methods C57Bl/6 mice were injected with either vehicle or a secretable form of adropin (450 nmol/kg, i.p.) three times over a 24-h period. The mice were fasted to accentuate the differences between animals in adropin plasma levels before their hearts were isolated and perfused using a working heart system. In addition, direct addition of adropin to the perfusate of ex vivo hearts isolated from non-fasting mice was utilized to investigate the acute effects of the peptide on heart metabolism and ex vivo function. Results In contrast to the observed fasting-induced predominance of fatty acid oxidation as a source of ATP production in control hearts, insulin inhibition of fatty acid oxidation was preserved by adropin treatment. Adropin-treated mouse hearts also showed a higher cardiac work, which was accompanied by improved cardiac efficiency and enhanced insulin signalling compared to control hearts. Interestingly, acute adropin administration to isolated working hearts also resulted in an inhibition of fatty acid oxidation, accompanied by a robust stimulation of glucose oxidation compared to vehicle-treated hearts. Adropin also increased activation of downstream cardiac insulin signalling. Moreover, both in vivo and ex vivo treatment protocols induced a reduction in the inhibitory phosphorylation of pyruvate dehydrogenase (PDH), the major enzyme of glucose oxidation, and the protein levels of the responsible kinase PDH kinase 4 and the insulin-signalling inhibitory phosphorylation of JNK (p-T183/Y185) and IRS-1 (p-S307), suggesting acute receptor- and/or post-translational modification-mediated mechanisms. Conclusions These results demonstrate that adropin has important effects on energy metabolism in the heart and may be a putative candidate for the treatment of cardiac disease associated with impaired insulin sensitivity.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
22h发布了新的文献求助10
2秒前
4秒前
时光的沙完成签到,获得积分20
5秒前
6秒前
满三江应助Jin采纳,获得10
7秒前
带你去喝雪碧完成签到 ,获得积分10
8秒前
CodeCraft应助kingripple采纳,获得10
9秒前
郭二发布了新的文献求助10
11秒前
12秒前
老白完成签到,获得积分10
12秒前
13秒前
14秒前
努力乘凉发布了新的文献求助30
15秒前
15秒前
Kwanman完成签到,获得积分10
16秒前
一一发布了新的文献求助10
17秒前
DQY发布了新的文献求助10
17秒前
Jin完成签到,获得积分10
17秒前
云峰发布了新的文献求助10
21秒前
24秒前
一一完成签到,获得积分20
24秒前
Simlove完成签到,获得积分10
24秒前
25秒前
Orange应助可靠的寒风采纳,获得10
26秒前
余红完成签到,获得积分10
26秒前
27秒前
Lucas应助hanleiharry1采纳,获得10
28秒前
lemon发布了新的文献求助20
28秒前
勤恳的嚓茶完成签到,获得积分10
28秒前
29秒前
29秒前
bkagyin应助科研通管家采纳,获得10
32秒前
情怀应助科研通管家采纳,获得10
32秒前
传奇3应助科研通管家采纳,获得10
32秒前
小马甲应助科研通管家采纳,获得10
32秒前
852应助科研通管家采纳,获得10
32秒前
景辣条应助科研通管家采纳,获得10
32秒前
CodeCraft应助科研通管家采纳,获得10
32秒前
我是老大应助科研通管家采纳,获得10
32秒前
大模型应助科研通管家采纳,获得10
32秒前
高分求助中
Spray / Wall-interaction Modelling by Dimensionless Data Analysis 2000
ALA生合成不全マウスでの糖代謝異常の分子機構解析 520
安全防范技术与工程 500
Mathematics and Finite Element Discretizations of Incompressible Navier—Stokes Flows 500
A real-time energy management strategy based on fuzzy control and ECMS for PHEVs 400
2024 Medicinal Chemistry Reviews 400
Актуализированная стратиграфическая схема триасовых отложений Прикаспийского региона. Объяснительная записка 360
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3191610
求助须知:如何正确求助?哪些是违规求助? 2840976
关于积分的说明 8030842
捐赠科研通 2504427
什么是DOI,文献DOI怎么找? 1337627
科研通“疑难数据库(出版商)”最低求助积分说明 638193
邀请新用户注册赠送积分活动 606684