Evidence map›Paper›PMID 31775868›Full record

ArticleLipids in health and disease2019

Angiotensin-converting enzyme 2 regulates endoplasmic reticulum stress and mitochondrial function to preserve skeletal muscle lipid metabolism.

Xi Cao, Xin-Meng Lu, Xiu Tuo, Jing-Yi Liu, Yi-Chen Zhang, Li-Ni Song, Zhi-Qiang Cheng, Jin-Kui Yang, Zhong Xin

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Lipids in health and disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.6field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 52 citations in OpenAlex.

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  19. Association ofFrontiers in cardiovascular medicine · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Xi CaoBeijing Key Laboratory of Diabetes Research and Care, Beijing Diabetes institute, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
Xin-Meng LuDepartment of Endocrinology, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.
Xiu TuoBeijing Key Laboratory of Diabetes Research and Care, Beijing Diabetes institute, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
Jing-Yi LiuBeijing Key Laboratory of Diabetes Research and Care, Beijing Diabetes institute, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
Yi-Chen ZhangBeijing Key Laboratory of Diabetes Research and Care, Beijing Diabetes institute, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
Li-Ni SongBeijing Key Laboratory of Diabetes Research and Care, Beijing Diabetes institute, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
Zhi-Qiang ChengDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Jin-Kui YangBeijing Key Laboratory of Diabetes Research and Care, Beijing Diabetes institute, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China. jinkui.yang@gmail.com.
Zhong XinBeijing Key Laboratory of Diabetes Research and Care, Beijing Diabetes institute, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China. xinz@medmail.com.cn.ORCID http://orcid.org/0000-0002-6840-1922
Beijing Tongren Hospital · CNCapital Medical University · CNJohns Hopkins University · US

Funding

Beijing Hospitals Authority Youth Programme QML20170205National Natural Science Foundation of China 81670774Precision Medicine Research, State Key Development Program, China 2017YFC0909600Scientific Research Fund of Beijing Tongren Hospital, Capital Medical University 2014-YJJ-GGL-040
6 · The paper itself

Abstract

objectiveEndoplasmic 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.

methodsThe 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 (ACCα, SREBP-1c, LXRα, CPT-1α, PGC-1α and PPARα), ER stress and mitochondrial function related genes (GRP78, eIF2α, 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 IKKβ/NFκB/IRS-1 pathway was determined using lysate sample from skeletal muscle of ACE2 knockout mice.

resultsACE2 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 IKKβ/NFκB/IRS-1 pathway in skeletal muscle.

conclusionsACE2 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.

Indexed as

Activating Transcription Factor 4Angiotensin-Converting Enzyme 2AnimalsCarnitine O-PalmitoyltransferaseEndoplasmic ReticulumEndoplasmic Reticulum Chaperone BiPEndoplasmic Reticulum StressEukaryotic Initiation Factor-2Gene Expression RegulationHeat-Shock ProteinsI-kappa B KinaseInsulin Receptor Substrate ProteinsInsulin ResistanceLipid MetabolismLiver X ReceptorsMaleAce2 protein, mouseActivating Transcription Factor 4Angiotensin-Converting Enzyme 2Atf4 protein, mouseBcl2 protein, mouseCarnitine O-PalmitoyltransferaseCPT1B protein, mouseEndoplasmic Reticulum Chaperone BiPEukaryotic Initiation Factor-2Heat-Shock ProteinsHspa5 protein, mouseI-kappa B KinaseIkbkb protein, mouseInsulin Receptor Substrate ProteinsIrs1 protein, mouseLiver X ReceptorsNF-kappa BPeptidyl-Dipeptidase APeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPPAR alphaPpara protein, mousePpargc1a protein, mouseProto-Oncogene Proteins c-bcl-2Srebf1 protein, mouseSterol Regulatory Element Binding Protein 1Succinate DehydrogenaseTriglyceridesACE2Endoplasmic reticulumIntramuscular fatMitochondrial function

Identifiers

PMID31775868
PMCPMC6882339
OpenAlexW2989747876

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.