Metformin and Resveratrol Inhibit Drp1-Mediated Mitochondrial Fission and Prevent ER Stress-Associated NLRP3 Inflammasome Activation in the Adipose Tissue of Diabetic Mice

Li, Aiyun; Zhang, Shuihong; Li, Jia; Liu, Kang; Huang, Fang; Liu, Baolin

doi:10.1016/j.mce.2016.06.008

Cited by 197Inflammasome and immune disordersAdipose Tissue and MetabolismSirtuins and Resveratrol in Medicine

Metformin and Resveratrol Inhibit Drp1-Mediated Mitochondrial Fission and Prevent ER Stress-Associated NLRP3 Inflammasome Activation in the Adipose Tissue of Diabetic Mice

Li, Aiyun, Zhang, Shuihong, Li, Jia, Liu, Kang, Huang, Fang, Liu, Baolin·2016·Molecular and Cellular Endocrinology

DOI 10.1016/j.mce.2016.06.008

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Abstract

Objective This study was designed to investigate the hypothesis that metformin and resveratrol exhibited the same effect on inhibition of NLRP3 inflammasome activation with regulation of AMPK in adipose tissue exposed to high glucose.Methods To induce adipose tissue dysfunction, we treated epididymal adipose tissue of mice or differentiated 3T3-L1 adipocytes with high glucose (33 mM) for 24 h. Meanwhile, mice were injected with streptozotocin STZ to induce diabetes and followed by oral administration of metformin (200 mg/kg), resveratrol (50 mg/kg) or ER stress inhibitor TUDCA (50 mg/kg) for 7 days. The effects of metformin and resveratrol on ROS production, mitochondrial fission, ER stress, TXNIP/NLRP3 inflammasome activation, inflammation and apoptosis were observed.Results Metformin and resveratrol inhibited ROS-associated mitochondrial fission by upregulating Drp1 phosphorylation (Ser 637) in an AMPK-dependent manner, and then suppressed ER stress indicated by dephosphorylation of IRE1α and eIF2α in the adipose tissue. As a result from suppressing TXNIP/NLRP3 inflammasome activation, metformin and resveratrol inhibited inflammation and reduced cell apoptosis in adipose tissue or adipocytes exposed to high glucose.Conclusion Metformin and resveratrol protected mitochondrial integrity by inhibiting Drp1 activity and prevented NLRP3 inflammasome activation by suppressing ER stress, and thereby protected adipose function from high glucose insult.

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Both metformin and resveratrol inhibit ROS-associated mitochondria fission.
“Interestingly, both metformin and the anti-oxidant, resveratrol, inhibit ROS-associated mitochondria fission (152).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [152]

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Authors: Li, A., Zhang, S., Li, J., Liu, K., Huang, F., & Liu, B.
Affiliations: China Pharmaceutical University (CN)
Corresponding author: Liu, Baolin
ORCID: Li, Jia
Liu, Kang
Venue: Molecular and Cellular Endocrinology
Publisher: Elsevier BV
Published: 2016-10
Volume: 434
Pages: 36-47
ISSN: 0303-7207 (ISSN-L)
DOI: 10.1016/j.mce.2016.06.008
OpenAlex: W2428504347
Cited by: 197
References: 28
Citations by year: 2026: 12 · 2025: 14 · 2024: 13 · 2023: 21 · 2022: 21 · 2021: 29 · 2020: 33 · 2019: 18 · 2018: 13 · 2017: 18 · 2016: 4
FWCI: 9.18
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Molecular and Cellular Endocrinology (publishedVersion)
PubMed (publishedVersion)
Funders: Pharmaceutical University, Nanjing, China
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Keywords: metformin, resveratrol, Drp1, mitochondrial fission, endoplasmic reticulum stress, NLRP3 inflammasome, TXNIP, AMPK, adipose tissue dysfunction, high glucose, type 2 diabetes, IRE1α, eIF2α, reactive oxygen species, adipocyte apoptosis, tauroursodeoxycholic acid
MeSH terms: NLR Family, Pyrin Domain-Containing 3 Protein, Resveratrol, Adipose Tissue, Animals, Cell Differentiation, Diabetes Mellitus, Experimental, Gene Expression Regulation, Metformin, Mitochondria, Phosphorylation, Stilbenes, Apoptosis, Reactive Oxygen Species, Dynamins, 3T3-L1 Cells, Mice, Inflammasomes, Endoplasmic Reticulum Stress, Mitochondrial Dynamics

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Metformin and Resveratrol Inhibit Drp1-Mediated Mitochondrial Fission and Prevent ER Stress-Associated NLRP3 Inflammasome Activation in the Adipose Tissue of Diabetic Mice

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