Systemic Oxidative Stress and Visceral Adipose Tissue Mediators of NLRP3 Inflammasome and Autophagy Are Reduced in Obese Type 2 Diabetic Patients Treated with Metformin
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
Affiliations
Zaida Abad-Jiménez
Department of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain
Sandra López-Domènech
Department of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain
Rubén Díaz-Rúa
Department of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain
Francesca Iannantuoni
Department of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain
Segundo Ángel Gómez-Abril
Department 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, Spain
Dolores Periañez-Gómez
Department 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, Spain
Carlos Morillas
Department of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain
Víctor M. Víctor
Department of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain
Milagros Rocha
Department of Endocrinology and Nutrition, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain
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.
