机构：[1]Beijing Key Laboratory of Diabetes Research and Care, Beijing Diabetesinstitute, Department of Endocrinology, Beijing Tongren Hospital, CapitalMedical University, Beijing 100730, China临床科室内分泌科首都医科大学附属北京同仁医院首都医科大学附属同仁医院[2]Department of Endocrinology,Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China[3]Department of Pharmacology and Molecular Sciences, Johns HopkinsUniversity School of Medicine, Baltimore, MD 21205, USA
Objective Endoplasmic reticulum (ER) stress and mitochondrial function affected intramuscular fat accumulation. However, there is no clear evident on the effect of the regulation of ER stress and mitochondrial function by Angiotensin-converting enzyme 2 (ACE2) on the prevention of intramuscular fat metabolism. We investigated the effects of ACE2 on ER stress and mitochondrial function in skeletal muscle lipid metabolism. Methods The triglyceride (TG) content in skeletal muscle of ACE2 knockout mice and Ad-ACE2-treated db/db mice were detected by assay kits. Meanwhile, the expression of lipogenic genes (ACC alpha, SREBP-1c, LXR alpha, CPT-1 alpha, PGC-1 alpha and PPAR alpha), ER stress and mitochondrial function related genes (GRP78, eIF2 alpha, ATF4, BCL-2, and SDH6) were analyzed by RT-PCR. Lipid metabolism, ER stress and mitochondrial function related genes were analyzed by RT-PCR in ACE2-overexpression C2C12 cell. Moreover, the IKK beta/NF kappa B/IRS-1 pathway was determined using lysate sample from skeletal muscle of ACE2 knockout mice. Results ACE2 deficiency in vivo is associated with increased lipid accumulation in skeletal muscle. The ACE2 knockout mice displayed an elevated level of ER stress and mitochondrial dysfunctions in skeletal muscle. In contrast, activation of ACE2 can ameliorate ER stress and mitochondrial function, which slightly accompanied by reduced TG content and down-regulated the expression of skeletal muscle lipogenic proteins in the db/db mice. Additionally, ACE2 improved skeletal muscle lipid metabolism and ER stress genes in the C2C12 cells. Mechanistically, endogenous ACE2 improved lipid metabolism through the IKK beta/NF kappa B/IRS-1 pathway in skeletal muscle. Conclusions ACE2 was first reported to play a notable role on intramuscular fat regulation by improving endoplasmic reticulum and mitochondrial function. This study may provide a strategy for treating insulin resistance in skeletal muscle.
基金：
Foundation of Precision Medicine Research, State Key Development Program, China [2017YFC0909600]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81670774]; Beijing Hospitals Authority Youth Programme [QML20170205]; Scientific Research Fund of Beijing Tongren Hospital, Capital Medical University [2014-YJJ-GGL-040]
第一作者机构：[1]Beijing Key Laboratory of Diabetes Research and Care, Beijing Diabetesinstitute, Department of Endocrinology, Beijing Tongren Hospital, CapitalMedical University, Beijing 100730, China
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推荐引用方式(GB/T 7714)：
Cao Xi,Lu Xin-Meng,Tuo Xiu,et al.Angiotensin-converting enzyme 2 regulates endoplasmic reticulum stress and mitochondrial function to preserve skeletal muscle lipid metabolism[J].LIPIDS IN HEALTH AND DISEASE.2019,18(1):doi:10.1186/s12944-019-1145-x.
APA：
Cao, Xi,Lu, Xin-Meng,Tuo, Xiu,Liu, Jing-Yi,Zhang, Yi-Chen...&Xin, Zhong.(2019).Angiotensin-converting enzyme 2 regulates endoplasmic reticulum stress and mitochondrial function to preserve skeletal muscle lipid metabolism.LIPIDS IN HEALTH AND DISEASE,18,(1)
MLA：
Cao, Xi,et al."Angiotensin-converting enzyme 2 regulates endoplasmic reticulum stress and mitochondrial function to preserve skeletal muscle lipid metabolism".LIPIDS IN HEALTH AND DISEASE 18..1(2019)
