Systemic Oxidative Stress and Visceral Adipose Tissue Mediators of NLRP3 Inflammasome and Autophagy Are Reduced in Obese Type 2 Diabetic Patients Treated with Metformin
Obesity is a low-grade inflammatory condition affecting a range of individuals, from metabolically healthy obese (MHO) subjects to type 2 diabetes (T2D) patients. Metformin has been shown to display anti-inflammatory properties, though the underlying molecular mechanisms are unclear. To study whethe...
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| Format: | Article |
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MDPI AG
2020-09-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/9/892 |
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| author | Zaida Abad-Jiménez Sandra López-Domènech Rubén Díaz-Rúa Francesca Iannantuoni Segundo Ángel Gómez-Abril Dolores Periañez-Gómez Carlos Morillas Víctor M. Víctor Milagros Rocha |
| author_facet | Zaida Abad-Jiménez Sandra López-Domènech Rubén Díaz-Rúa Francesca Iannantuoni Segundo Ángel Gómez-Abril Dolores Periañez-Gómez Carlos Morillas Víctor M. Víctor Milagros Rocha |
| author_sort | Zaida Abad-Jiménez |
| collection | DOAJ |
| description | Obesity is a low-grade inflammatory condition affecting a range of individuals, from metabolically healthy obese (MHO) subjects to type 2 diabetes (T2D) patients. Metformin has been shown to display anti-inflammatory properties, though the underlying molecular mechanisms are unclear. To study whether the effects of metformin are mediated by changes in the inflammasome complex and autophagy in visceral adipose tissue (VAT) of obese patients, a biopsy of VAT was obtained from a total of 68 obese patients undergoing gastric bypass surgery. The patients were clustered into two groups: MHO patients and T2D patients treated with metformin. Patients treated with metformin showed decreased levels of all analyzed serum pro-inflammatory markers (TNFα, IL6, IL1β and MCP1) and a downwards trend in IL18 levels associated with a lower production of oxidative stress markers in leukocytes (mitochondrial ROS and myeloperoxidase (MPO)). A reduction in protein levels of MCP1, NFκB, NLRP3, ASC, ATG5, Beclin1 and CHOP and an increase in p62 were also observed in the VAT of the diabetic group. This downregulation of both the NLRP3 inflammasome and autophagy in VAT may be associated with the improved inflammatory profile and leukocyte homeostasis seen in obese T2D patients treated with metformin with respect to MHO subjects and endorses the cardiometabolic protective effect of this drug. |
| first_indexed | 2024-03-10T16:11:56Z |
| format | Article |
| id | doaj.art-c5f3ab13b7174a88916073eff73b9f6b |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T16:11:56Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-c5f3ab13b7174a88916073eff73b9f6b2023-11-20T14:26:42ZengMDPI AGAntioxidants2076-39212020-09-019989210.3390/antiox9090892Systemic Oxidative Stress and Visceral Adipose Tissue Mediators of NLRP3 Inflammasome and Autophagy Are Reduced in Obese Type 2 Diabetic Patients Treated with MetforminZaida Abad-Jiménez0Sandra López-Domènech1Rubén Díaz-Rúa2Francesca Iannantuoni3Segundo Ángel Gómez-Abril4Dolores Periañez-Gómez5Carlos Morillas6Víctor M. Víctor7Milagros Rocha8Department of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, SpainDepartment of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, SpainDepartment of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, SpainDepartment of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, SpainDepartment of General and Digestive System Surgery, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, SpainDepartment of General and Digestive System Surgery, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, SpainDepartment of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, SpainDepartment of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, SpainDepartment of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, SpainObesity is a low-grade inflammatory condition affecting a range of individuals, from metabolically healthy obese (MHO) subjects to type 2 diabetes (T2D) patients. Metformin has been shown to display anti-inflammatory properties, though the underlying molecular mechanisms are unclear. To study whether the effects of metformin are mediated by changes in the inflammasome complex and autophagy in visceral adipose tissue (VAT) of obese patients, a biopsy of VAT was obtained from a total of 68 obese patients undergoing gastric bypass surgery. The patients were clustered into two groups: MHO patients and T2D patients treated with metformin. Patients treated with metformin showed decreased levels of all analyzed serum pro-inflammatory markers (TNFα, IL6, IL1β and MCP1) and a downwards trend in IL18 levels associated with a lower production of oxidative stress markers in leukocytes (mitochondrial ROS and myeloperoxidase (MPO)). A reduction in protein levels of MCP1, NFκB, NLRP3, ASC, ATG5, Beclin1 and CHOP and an increase in p62 were also observed in the VAT of the diabetic group. This downregulation of both the NLRP3 inflammasome and autophagy in VAT may be associated with the improved inflammatory profile and leukocyte homeostasis seen in obese T2D patients treated with metformin with respect to MHO subjects and endorses the cardiometabolic protective effect of this drug.https://www.mdpi.com/2076-3921/9/9/892visceral adipose tissue (VAT)obesitytype 2 diabetes (T2D)inflammatory cytokinesautophagyoxidative stress |
| spellingShingle | Zaida Abad-Jiménez Sandra López-Domènech Rubén Díaz-Rúa Francesca Iannantuoni Segundo Ángel Gómez-Abril Dolores Periañez-Gómez Carlos Morillas Víctor M. Víctor Milagros Rocha Systemic Oxidative Stress and Visceral Adipose Tissue Mediators of NLRP3 Inflammasome and Autophagy Are Reduced in Obese Type 2 Diabetic Patients Treated with Metformin Antioxidants visceral adipose tissue (VAT) obesity type 2 diabetes (T2D) inflammatory cytokines autophagy oxidative stress |
| title | Systemic Oxidative Stress and Visceral Adipose Tissue Mediators of NLRP3 Inflammasome and Autophagy Are Reduced in Obese Type 2 Diabetic Patients Treated with Metformin |
| title_full | Systemic Oxidative Stress and Visceral Adipose Tissue Mediators of NLRP3 Inflammasome and Autophagy Are Reduced in Obese Type 2 Diabetic Patients Treated with Metformin |
| title_fullStr | Systemic Oxidative Stress and Visceral Adipose Tissue Mediators of NLRP3 Inflammasome and Autophagy Are Reduced in Obese Type 2 Diabetic Patients Treated with Metformin |
| title_full_unstemmed | Systemic Oxidative Stress and Visceral Adipose Tissue Mediators of NLRP3 Inflammasome and Autophagy Are Reduced in Obese Type 2 Diabetic Patients Treated with Metformin |
| title_short | Systemic Oxidative Stress and Visceral Adipose Tissue Mediators of NLRP3 Inflammasome and Autophagy Are Reduced in Obese Type 2 Diabetic Patients Treated with Metformin |
| title_sort | systemic oxidative stress and visceral adipose tissue mediators of nlrp3 inflammasome and autophagy are reduced in obese type 2 diabetic patients treated with metformin |
| topic | visceral adipose tissue (VAT) obesity type 2 diabetes (T2D) inflammatory cytokines autophagy oxidative stress |
| url | https://www.mdpi.com/2076-3921/9/9/892 |
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