Evidence map›Paper›PMID 39334359›Full record

ArticleLipids in health and disease2024

Empagliflozin alleviates obesity-related cardiac dysfunction via the activation of SIRT3-mediated autophagosome formation.

Youhong Luo, Tongtong Ye, Hongzhan Tian, Hongwei Song, Chengxia Kan, Fang Han, Ningning Hou, Xiaodong Sun, Jingwen Zhang

Abstract read
In one paragraph

Article in Lipids in health and disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
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

9 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Review
  9. Review
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.

Youhong Luo *Department of Endocrinology and Metabolism, Clinical Research Center, Shandong Provincial Key Medical and Health Discipline of Endocrinology, Affiliated Hospital of Shandong Second Medical University, Weifang, 261031, China.
Tongtong Ye *Department of Endocrinology and Metabolism, Clinical Research Center, Shandong Provincial Key Medical and Health Discipline of Endocrinology, Affiliated Hospital of Shandong Second Medical University, Weifang, 261031, China.
Hongzhan TianDepartment of Endocrinology and Metabolism, Clinical Research Center, Shandong Provincial Key Medical and Health Discipline of Endocrinology, Affiliated Hospital of Shandong Second Medical University, Weifang, 261031, China.
Hongwei SongDepartment of Endocrinology and Metabolism, Clinical Research Center, Shandong Provincial Key Medical and Health Discipline of Endocrinology, Affiliated Hospital of Shandong Second Medical University, Weifang, 261031, China.
Chengxia KanDepartment of Endocrinology and Metabolism, Clinical Research Center, Shandong Provincial Key Medical and Health Discipline of Endocrinology, Affiliated Hospital of Shandong Second Medical University, Weifang, 261031, China.
Fang HanDepartment of Endocrinology and Metabolism, Clinical Research Center, Shandong Provincial Key Medical and Health Discipline of Endocrinology, Affiliated Hospital of Shandong Second Medical University, Weifang, 261031, China.
Ningning HouDepartment of Endocrinology and Metabolism, Clinical Research Center, Shandong Provincial Key Medical and Health Discipline of Endocrinology, Affiliated Hospital of Shandong Second Medical University, Weifang, 261031, China.
Xiaodong SunDepartment of Endocrinology and Metabolism, Clinical Research Center, Shandong Provincial Key Medical and Health Discipline of Endocrinology, Affiliated Hospital of Shandong Second Medical University, Weifang, 261031, China. xiaodong.sun@sdsmu.edu.cn.ORCID https://orcid.org/0000-0001-7775-2823
Jingwen ZhangDepartment of Endocrinology and Metabolism, Clinical Research Center, Shandong Provincial Key Medical and Health Discipline of Endocrinology, Affiliated Hospital of Shandong Second Medical University, Weifang, 261031, China. fyjwzhang@sdsmu.edu.cn.ORCID https://orcid.org/0000-0002-6064-1374

Funding

National Natural Science Foundation of China 82170865Shandong Province Medical and Health Science and Technology Development Project 202203060805Shandong Province Medical and Health Science and Technology Development Project 202203060917Taishan Scholars Project of Shandong Province tsqn202211365
6 · The paper itself

Abstract

backgroundEmpagliflozin (EMPA) has demonstrated efficacy in providing cardiovascular benefits in metabolic diseases. However, the direct effect of EMPA on autophagy in obesity-related cardiac dysfunction remains unclear. Therefore, this study aimed to determine changes in cardiac autophagy during diet-induced obesity and clarify the exact mechanism by which EMPA regulates autophagic pathways.

methodsMale C57BL/6J mice were fed a 12-week high-fat diet (HFD) followed by 8 weeks of EMPA treatment. Body composition analysis and echocardiography were performed to evaluate metabolic alterations and cardiac function. Histological and immunofluorescence staining was used to evaluate potential enhancements in myocardial structure and biological function. Additionally, H9c2 cells were transfected with small interfering RNA targeting sirtuin 3 (SIRT3) and further treated with palmitic acid (PA) with or without EMPA. Autophagy-related targets were analyzed by western blotting and RT‒qPCR.

resultsEMPA administration effectively ameliorated metabolic disorders and cardiac diastolic dysfunction in HFD-fed mice. EMPA prevented obesity-induced myocardial hypertrophy, fibrosis, and inflammation through the activation of SIRT3-mediated autophagosome formation. The upregulation of SIRT3 triggered by EMPA promoted the initiation of autophagy by activating AMP-activated protein kinase (AMPK) and Beclin1. Furthermore, activated SIRT3 contributed to the elongation of autophagosomes through autophagy-related 4B cysteine peptidase (ATG4B) and autophagy-related 5 (ATG5).

conclusionsEMPA promotes SIRT3-mediated autophagosome formation to alleviate damage to the cardiac structure and function of obese mice. Activated SIRT3 initiates autophagy through AMPK/Beclin1 and further stimulates elongation of the autophagosome membrane via ATG4B/ATG5. These results provide a new explanation for the cardioprotective benefits of EMPA in obesity.

Indexed as

AutophagosomesAutophagyBenzhydryl CompoundsDiet, High-FatGlucosidesMice, Inbred C57BLObesitySirtuin 3AMP-Activated Protein KinasesAnimalsCell LineMaleMiceMyocardiumMyocytes, CardiacSodium-Glucose Transporter 2 InhibitorsAMP-Activated Protein KinasesBenzhydryl CompoundsempagliflozinGlucosidesSirt3 protein, mouseSirtuin 3Sodium-Glucose Transporter 2 InhibitorsAutophagyEmpagliflozinObesity-related cardiac dysfunctionSIRT3

Identifiers

PMID39334359
PMCPMC11430456

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.