PMID- 31647926
OWN - NLM
STAT- MEDLINE
DCOM- 20200701
LR  - 20200826
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 170
DP  - 2019 Dec
TI  - Empagliflozin reduces the levels of CD36 and cardiotoxic lipids while improving 
      autophagy in the hearts of Zucker diabetic fatty rats.
PG  - 113677
LID - S0006-2952(19)30376-4 [pii]
LID - 10.1016/j.bcp.2019.113677 [doi]
AB  - The EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcome Event Trial in 
      patients with Type 2 Diabetes Mellitus (T2DM)) trial made evident the 
      potentiality of pharmacological sodium-glucose cotransporter 2 (SGLT2) inhibition 
      for treating patients with diabetes and cardiovascular disease. Since the effect 
      of empagliflozin or other SGLT2 inhibitors on the whole cardiac metabolic profile 
      was never analysed before, and with the purpose to contribute to elucidate the 
      benefits at cardiac level of the use of empagliflozin, we explored the effect of 
      the treatment with empagliflozin for six weeks on the cardiac metabolomic profile 
      of Zucker diabetic fatty rats, a model of early stage T2DM, using untargeted 
      metabolomics approach. Empagliflozin reduced significantly the cardiac content of 
      sphingolipids (ceramides and sphingomyelins) and glycerophospholipids (major 
      bioactive contributing factors linking insulin resistance to cardiac damage) and 
      decreased the cardiac content of the fatty acid transporter cluster of 
      differentiation 36 (CD36); induced significant decreases of the cardiac levels of 
      essential glycolysis intermediaries 2,3-bisphosphoglycerate and 
      phosphoenolpyruvate, and regulated the abundance of several amino acids of 
      relevance as tricarboxylic acid suppliers and/or in the metabolic control of the 
      cardiac function as glutamic acid, gamma-aminobutyric acid and sarcosine. 
      Empagliflozin treatment activated the cardioprotective master regulator of 
      cellular energyhomeostasis AMP-activatedproteinkinase (AMPK) and enhanced 
      autophagy at cardiac level, while it decreased significantly the cardiac mRNA 
      levels of the pro-inflammatory cytokines interleukin-6 (IL-6), chemerin, TNF-alpha 
      and MCP-1, reinforcing the hypothesis of a direct role for empagliflozin in 
      attenuating cardiac inflammation. Our results provide an advancement on the 
      knowledge of the mechanisms linking the therapy with empagliflozin with 
      protective effects on the development of cardiometabolic diseases whose course is 
      associated with remarkable cardiac bioenergetics dysregulation and disarrangement 
      in cardiac metabolome and lipidome.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
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/Servicio Gallego de Salud 
      (XXIS/SERGAS), Santiago de Compostela, Spain; Centro de Investigacion Biomedica 
      en Red de Enfermedades Cardiovasculares (CIBERCV), Institute of Health Carlos 
      III, 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/Servicio Gallego de Salud 
      (XXIS/SERGAS), Santiago de Compostela, Spain; Centro de Investigacion Biomedica 
      en Red de Enfermedades Cardiovasculares (CIBERCV), Institute of Health Carlos 
      III, Spain. Electronic address: sandra.feijoo.bandin@sergas.es.
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/Servicio Gallego de Salud 
      (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, 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, Spain.
FAU - Gil-Longo, Jose
AU  - Gil-Longo J
AD  - Group of Pharmacology of Chronic Diseases (CD Pharma), Department of 
      Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de 
      Compostela, Spain.
FAU - Costa Pereira, Thiago M
AU  - Costa Pereira TM
AD  - Group of Pharmacology of Chronic Diseases (CD Pharma), Department of 
      Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de 
      Compostela, Spain; Pharmaceutical Sciences Graduate Program, Federal Institute of 
      Education, Science and Technology (IFES), Vila Velha, ES, Brazil.
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 - Rodriguez-Segade, Santiago
AU  - Rodriguez-Segade S
AD  - Department of Biochemistry and Molecular Biology, University of Santiago de 
      Compostela, Spain; Clinical Biochemistry Laboratory, Xerencia de Xestion 
      Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, Spain.
FAU - Rodriguez, Javier
AU  - Rodriguez J
AD  - Clinical Biochemistry Laboratory, Xerencia de Xestion Integrada de Santiago 
      (XXIS/SERGAS), Santiago de Compostela, Spain.
FAU - Tarazon, Estefania
AU  - Tarazon E
AD  - Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares 
      (CIBERCV), Institute of Health Carlos III, Spain; 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, Spain; 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, Spain; 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 - 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/Servicio Gallego de Salud 
      (XXIS/SERGAS), Santiago de Compostela, Spain; Centro de Investigacion Biomedica 
      en Red de Enfermedades Cardiovasculares (CIBERCV), Institute of Health Carlos 
      III, 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/Servicio Gallego de Salud 
      (XXIS/SERGAS), Santiago de Compostela, Spain; Centro de Investigacion Biomedica 
      en Red de Enfermedades Cardiovasculares (CIBERCV), Institute of Health Carlos 
      III, Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191021
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (CD36 Antigens)
RN  - 0 (Cd36 protein, rat)
RN  - 0 (Glucosides)
RN  - 0 (Slc5a2 protein, rat)
RN  - 0 (Sodium-Glucose Transporter 2)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - HDC1R2M35U (empagliflozin)
SB  - IM
MH  - Animals
MH  - Autophagy/drug effects/*physiology
MH  - Benzhydryl Compounds/*pharmacology
MH  - Body Composition/drug effects/physiology
MH  - CD36 Antigens/antagonists & inhibitors/*metabolism
MH  - Glucosides/*pharmacology
MH  - Heart/drug effects
MH  - Lipid Metabolism/drug effects/*physiology
MH  - Male
MH  - Myocardium/*metabolism
MH  - Rats
MH  - Rats, Zucker
MH  - Sodium-Glucose Transporter 2/metabolism
MH  - Sodium-Glucose Transporter 2 Inhibitors/*pharmacology
OTO - NOTNLM
OT  - Ceramides
OT  - Empagliflozin
OT  - Glycerophospholipids
OT  - Heart
OT  - Metabolomics
OT  - Sphingolipids
EDAT- 2019/10/28 06:00
MHDA- 2020/07/02 06:00
CRDT- 2019/10/25 06:00
PHST- 2019/08/27 00:00 [received]
PHST- 2019/10/17 00:00 [accepted]
PHST- 2019/10/28 06:00 [pubmed]
PHST- 2020/07/02 06:00 [medline]
PHST- 2019/10/25 06:00 [entrez]
AID - S0006-2952(19)30376-4 [pii]
AID - 10.1016/j.bcp.2019.113677 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2019 Dec;170:113677. doi: 10.1016/j.bcp.2019.113677. Epub 2019 
      Oct 21.