PMID- 35185578 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220223 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 13 DP - 2022 TI - The Treatment With the SGLT2 Inhibitor Empagliflozin Modifies the Hepatic Metabolome of Male Zucker Diabetic Fatty Rats Towards a Protective Profile. PG - 827033 LID - 10.3389/fphar.2022.827033 [doi] LID - 827033 AB - The EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcome Event Trial in patients with Type 2 Diabetes Mellitus (T2DM)) trial evidenced the potential of sodium-glucose cotransporter 2 (SGLT2) inhibitors for the treatment of patients with diabetes and cardiovascular disease. Recent evidences have shown the benefits of the SGLT2 inhibitor empagliflozin on improving liver steatosis and fibrosis in patients with T2DM. Metabolomic studies have been shown to be very useful to improve the understanding of liver pathophysiology during the development and progression of metabolic hepatic diseases, and because the effects of empagliflozin and of other SGLT2 inhibitors on the complete metabolic profile of the liver has never been analysed before, we decided to study the impact on the liver of male Zucker diabetic fatty (ZDF) rats of a treatment for 6 weeks with empagliflozin using an untargeted metabolomics approach, with the purpose to help to clarify the benefits of the use of empagliflozin at hepatic level. We found that empagliflozin is able to change the hepatic lipidome towards a protective profile, through an increase of monounsaturated and polyunsaturated glycerides, phosphatidylcholines, phosphatidylethanolamines, lysophosphatidylinositols and lysophosphatidylcholines. Empagliflozin also induces a decrease in the levels of the markers of inflammation IL-6, chemerin and chemerin receptor in the liver. Our results provide new evidences regarding the molecular pathways through which empagliflozin could exert hepatoprotector beneficial effects in T2DM. CI - Copyright (c) 2022 Aragon-Herrera, Otero-Santiago, Anido-Varela, Morana-Fernandez, Campos-Toimil, Garcia-Caballero, Barral, Tarazon, Rosello-Lleti, Portoles, Gualillo, Moscoso, Lage, Gonzalez-Juanatey, Feijoo-Bandin and Lago. FAU - Aragon-Herrera, Alana AU - Aragon-Herrera A AD - Cellular and Molecular Cardiology Research Unit, Institute of Biomedical Research and Xerencia de Xestion Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, Spain. AD - Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Institute of Health Carlos III, Madrid, Spain. FAU - Otero-Santiago, Manuel AU - Otero-Santiago M AD - Cellular and Molecular Cardiology Research Unit, Institute of Biomedical Research and Xerencia de Xestion Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, Spain. FAU - Anido-Varela, Laura AU - Anido-Varela L AD - Cellular and Molecular Cardiology Research Unit, Institute of Biomedical Research and Xerencia de Xestion Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, Spain. FAU - Morana-Fernandez, Sandra AU - Morana-Fernandez S AD - Cellular and Molecular Cardiology Research Unit, Institute of Biomedical Research and Xerencia de Xestion Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, Spain. FAU - Campos-Toimil, Manuel AU - Campos-Toimil M AD - Group of Pharmacology of Chronic Diseases (CD Pharma), Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, Santiago de Compostela, Spain. FAU - Garcia-Caballero, Tomas AU - Garcia-Caballero T AD - Department of Morphological Sciences, University of Santiago de Compostela and Xerencia de Xestion Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, Spain. FAU - Barral, Luis AU - Barral L AD - Group of Polymers, Department of Physics and Earth Sciences, University of La Coruna, La Coruna, Spain. FAU - Tarazon, Estefania AU - Tarazon E AD - Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Institute of Health Carlos III, Madrid, Spain. AD - Cardiocirculatory Unit, Health Research Institute of La Fe University Hospital, Valencia, Spain. FAU - Rosello-Lleti, Esther AU - Rosello-Lleti E AD - Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Institute of Health Carlos III, Madrid, Spain. AD - Cardiocirculatory Unit, Health Research Institute of La Fe University Hospital, Valencia, Spain. FAU - Portoles, Manuel AU - Portoles M AD - Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Institute of Health Carlos III, Madrid, Spain. AD - Cardiocirculatory Unit, Health Research Institute of La Fe University Hospital, Valencia, Spain. FAU - Gualillo, Oreste AU - Gualillo O AD - Laboratory of Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases, Institute of Biomedical Research and Xerencia de Xestion Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, Spain. FAU - Moscoso, Isabel AU - Moscoso I AD - Cardiology Group, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS) and Institute of Biomedical Research of Santiago de Compostela (IDIS-SERGAS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain. FAU - Lage, Ricardo AU - Lage R AD - Cardiology Group, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS) and Institute of Biomedical Research of Santiago de Compostela (IDIS-SERGAS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain. FAU - Gonzalez-Juanatey, Jose Ramon AU - Gonzalez-Juanatey JR AD - Cellular and Molecular Cardiology Research Unit, Institute of Biomedical Research and Xerencia de Xestion Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, Spain. AD - Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Institute of Health Carlos III, Madrid, Spain. FAU - Feijoo-Bandin, Sandra AU - Feijoo-Bandin S AD - Cellular and Molecular Cardiology Research Unit, Institute of Biomedical Research and Xerencia de Xestion Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, Spain. AD - Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Institute of Health Carlos III, Madrid, Spain. FAU - Lago, Francisca AU - Lago F AD - Cellular and Molecular Cardiology Research Unit, Institute of Biomedical Research and Xerencia de Xestion Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, Spain. AD - Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Institute of Health Carlos III, Madrid, Spain. LA - eng PT - Journal Article DEP - 20220202 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC8847595 OTO - NOTNLM OT - diabetes OT - empagliflozin OT - inflammation OT - liver OT - metabolome COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/02/22 06:00 MHDA- 2022/02/22 06:01 PMCR- 2022/02/02 CRDT- 2022/02/21 06:00 PHST- 2021/12/09 00:00 [received] PHST- 2022/01/04 00:00 [accepted] PHST- 2022/02/21 06:00 [entrez] PHST- 2022/02/22 06:00 [pubmed] PHST- 2022/02/22 06:01 [medline] PHST- 2022/02/02 00:00 [pmc-release] AID - 827033 [pii] AID - 10.3389/fphar.2022.827033 [doi] PST - epublish SO - Front Pharmacol. 2022 Feb 2;13:827033. doi: 10.3389/fphar.2022.827033. eCollection 2022.