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
oldchen完成签到 ,获得积分10
1秒前
游一完成签到,获得积分10
3秒前
huang完成签到,获得积分10
4秒前
天天快乐应助无限的板栗采纳,获得10
4秒前
满意绿柳完成签到,获得积分10
4秒前
5秒前
woshihu发布了新的文献求助10
6秒前
yuanzizz完成签到,获得积分10
6秒前
端午瑾完成签到,获得积分10
10秒前
10秒前
Billy应助蘑菇采纳,获得10
10秒前
10秒前
Aijh完成签到,获得积分20
10秒前
euphoria完成签到,获得积分10
12秒前
12秒前
LGG发布了新的文献求助10
13秒前
13秒前
兴奋的平松完成签到,获得积分10
14秒前
Aijh发布了新的文献求助10
14秒前
14秒前
Leo完成签到,获得积分10
15秒前
冉木木完成签到,获得积分20
15秒前
钮小妞发布了新的文献求助30
16秒前
Wu完成签到,获得积分10
17秒前
18秒前
抹不掉的记忆完成签到,获得积分10
18秒前
18秒前
Lsx完成签到 ,获得积分10
19秒前
七个泡芙完成签到,获得积分20
19秒前
所所应助简单采纳,获得10
19秒前
满意绿柳发布了新的文献求助10
20秒前
才才完成签到 ,获得积分10
20秒前
21秒前
逍遥完成签到,获得积分10
21秒前
22秒前
菠菜菜str完成签到,获得积分10
22秒前
23秒前
shelley发布了新的文献求助10
24秒前
sixone完成签到,获得积分10
24秒前
充电宝应助hhh采纳,获得10
24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
Aspects of Babylonian celestial divination: the lunar eclipse tablets of Enūma Anu Enlil 500
Mathematics and Finite Element Discretizations of Incompressible Navier—Stokes Flows 500
2024 Medicinal Chemistry Reviews 400
Dictionary of socialism 350
Mixed-anion Compounds 300
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 3197655
求助须知:如何正确求助?哪些是违规求助? 2846449
关于积分的说明 8059235
捐赠科研通 2511321
什么是DOI,文献DOI怎么找? 1343271
科研通“疑难数据库(出版商)”最低求助积分说明 639536
邀请新用户注册赠送积分活动 609111