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
刚刚
充电宝应助科研小白采纳,获得10
刚刚
李健的粉丝团团长应助mmmm采纳,获得10
刚刚
bull发布了新的文献求助10
刚刚
1秒前
zyx发布了新的文献求助10
2秒前
2秒前
2秒前
新雨发布了新的文献求助10
3秒前
liwang发布了新的文献求助10
4秒前
xuxiangjin应助傲娇豪采纳,获得20
5秒前
王俊发布了新的文献求助10
5秒前
大米粒完成签到 ,获得积分20
6秒前
Ryo完成签到,获得积分10
6秒前
恶恶么v完成签到,获得积分10
6秒前
6秒前
lx33101128发布了新的文献求助10
7秒前
哇咔咔发布了新的文献求助10
7秒前
华仔应助bull采纳,获得10
7秒前
12345完成签到,获得积分10
8秒前
8秒前
8秒前
HongY完成签到,获得积分10
9秒前
Lucas应助正直的千柔采纳,获得10
10秒前
徐矜发布了新的文献求助10
11秒前
科研小白发布了新的文献求助10
11秒前
希望天下0贩的0应助12345采纳,获得10
13秒前
leyellows发布了新的文献求助10
13秒前
13秒前
14秒前
冯万里完成签到 ,获得积分10
16秒前
when发布了新的文献求助10
17秒前
王二哈完成签到,获得积分10
17秒前
酷酷发布了新的文献求助10
18秒前
不配.应助Chenqzl采纳,获得10
19秒前
甜刊关注了科研通微信公众号
20秒前
Gyaz发布了新的文献求助10
21秒前
Yuuuu完成签到 ,获得积分10
21秒前
22秒前
23秒前
高分求助中
Spray / Wall-interaction Modelling by Dimensionless Data Analysis 2000
Evolution 3rd edition 1500
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 700
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 700
ALA生合成不全マウスでの糖代謝異常の分子機構解析 520
Mathematics and Finite Element Discretizations of Incompressible Navier—Stokes Flows 500
A new species of Coccus (Homoptera: Coccoidea) from Malawi 500
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 3187919
求助须知:如何正确求助?哪些是违规求助? 2837554
关于积分的说明 8016013
捐赠科研通 2500266
什么是DOI,文献DOI怎么找? 1334820
科研通“疑难数据库(出版商)”最低求助积分说明 637305
邀请新用户注册赠送积分活动 605302