title: Glucose uptake and lipid metabolism are impaired in epicardial adipose tissue from heart failure patients with or without diabetes.
abstract: Type 2 diabetes mellitus is a complex metabolic disease, and cardiovascular disease is a leading complication of diabetes. Epicardial adipose tissue surrounding the heart displays biochemical, thermogenic, and cardioprotective properties. However, the metabolic cross-talk between epicardial fat and the myocardium is largely unknown. This study sought to understand epicardial adipose tissue metabolism from heart failure patients with or without diabetes. We aimed to unravel possible differences in glucose and lipid metabolism between human epicardial and subcutaneous adipocytes and elucidate the potential underlying mechanisms involved in heart failure. Insulin-stimulated [(14)C]glucose uptake and isoproterenol-stimulated lipolysis were measured in isolated epicardial and subcutaneous adipocytes. The expression of genes involved in glucose and lipid metabolism was analyzed by reverse transcription-polymerase chain reaction in adipocytes. In addition, epicardial and subcutaneous fatty acid composition was analyzed by high-resolution proton nuclear magnetic resonance spectroscopy. The difference between basal and insulin conditions in glucose uptake was significantly decreased (P= 0.006) in epicardial compared with subcutaneous adipocytes. Moreover, a significant (P< 0.001) decrease in the isoproterenol-stimulated lipolysis was also observed when the two fat depots were compared, and it was strongly correlated with lipolysis, lipid storage, and inflammation-related gene expression. Moreover, the fatty acid composition of these tissues was significantly altered by diabetes. These results emphasize potential metabolic differences between both fat depots in the presence of heart failure and highlight epicardial fat as a possible therapeutic target in situ in the cardiac microenvironment.
authors.affiliation: Center of Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal;
authors.forename: Ana
authors.initials: A
authors.lastname: Burgeiro
authors.affiliation: Center of Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal;
authors.forename: Amelia
authors.initials: A
authors.lastname: Fuhrmann
authors.affiliation: Faculty of Integrative Sciences and Technology, Quest International University Perak, Perak, Malaysia;
authors.forename: Sam
authors.initials: S
authors.lastname: Cherian
authors.affiliation: Center of Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal;
authors.forename: Daniel
authors.initials: D
authors.lastname: Espinoza
authors.affiliation: Center of Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal;
authors.forename: Ivana
authors.initials: I
authors.lastname: Jarak
authors.affiliation: Center of Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal; ecarvalh@cnc.uc.pt.
authors.forename: Rui A
authors.initials: RA
authors.lastname: Carvalho
authors.affiliation: Laboratory of Biostatistics and Medical Informatics, IBILI - Faculty of Medicine, University of Coimbra, Coimbra, Portugal;
authors.forename: Marisa
authors.initials: M
authors.lastname: Loureiro
authors.affiliation: Laboratory of Biostatistics and Medical Informatics, IBILI - Faculty of Medicine, University of Coimbra, Coimbra, Portugal;
authors.forename: Miguel
authors.initials: M
authors.lastname: Patrício
authors.affiliation: Cardiothroracic Surgery Unit at the University Hospital of Coimbra, Coimbra, Portugal;
authors.forename: Manuel
authors.initials: M
authors.lastname: Antunes
authors.affiliation: Center of Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Portuguese Diabetes Association, Lisbon, Portugal; Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas; and Arkansas Children's Hospital Research Institute, Little Rock, Arkansas.
authors.forename: Eugénia
authors.initials: E
authors.lastname: Carvalho
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006333:Heart Failure / Q000150:complications / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology*; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010496:Pericardium / Q000378:metabolism*
chemical_list: D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D002250:Carbon Radioisotopes; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D007328:Insulin; D005947:Glucose; D007545:Isoproterenol
keywords: diabetes; epicardial adipose tissue; glucose uptake; heart failure; lipolysis
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