title: Secretory products of guinea pig epicardial fat induce insulin resistance and impair primary adult rat cardiomyocyte function.
abstract: Epicardial adipose tissue (EAT) has been implicated in the development of heart disease. Nonetheless, the crosstalk between factors secreted from EAT and cardiomyocytes has not been studied. Here, we examined the effect of factors secreted from EAT on contractile function and insulin signalling in primary rat cardiomocytes. EAT and subcutaneous adipose tissue (SAT) were isolated from guinea pigs fed a high-fat (HFD) or standard diet. HFD feeding for 6 months induced glucose intolerance, and decreased fractional shortening and ejection fraction (all P < 0.05). Conditioned media (CM) generated from EAT and SAT explants were subjected to cytokine profiling using antibody arrays, or incubated with cardiomyocytes to assess the effects on insulin action and contractile function. Eleven factors were differentially secreted by EAT when compared to SAT. Furthermore, secretion of 30 factors by EAT was affected by HFD feeding. Most prominently, activin A-immunoreactivity was 6.4-fold higher in CM from HFD versus standard diet-fed animals and, 2-fold higher in EAT versus SAT. In cardiomyocytes, CM from EAT of HFD-fed animals increased SMAD2-phosphorylation, a marker for activin A-signalling, decreased sarcoplasmic-endoplasmic reticulum calcium ATPase 2a expression, and reduced insulin-mediated phosphorylation of Akt-Ser473 versus CM from SAT and standard diet-fed animals. Finally, CM from EAT of HFD-fed animals as compared to CM from the other groups markedly reduced sarcomere shortening and cytosolic Ca(2+)  fluxes in cardiomyocytes. These data provide evidence for an interaction between factors secreted from EAT and cardiomyocyte function.
authors.affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Centre, Düsseldorf, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Greulich
authors.forename: Daniella Herzfeld
authors.initials: DH
authors.lastname: de Wiza
authors.forename: Sebastian
authors.initials: S
authors.lastname: Preilowski
authors.forename: Zhaoping
authors.initials: Z
authors.lastname: Ding
authors.forename: Heidi
authors.initials: H
authors.lastname: Mueller
authors.forename: Dominique
authors.initials: D
authors.lastname: Langin
authors.forename: Kornelia
authors.initials: K
authors.lastname: Jaquet
authors.forename: D Margriet
authors.initials: DM
authors.lastname: Ouwens
authors.forename: Juergen
authors.initials: J
authors.lastname: Eckel
mesh_terms: D028341:Activins / Q000096:biosynthesis; D000818:Animals; D002118:Calcium / Q000032:analysis; D002318:Cardiovascular Diseases / Q000150:complications; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D004041:Dietary Fats; D006168:Guinea Pigs; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D032383:Myocytes, Cardiac / Q000473:pathology / Q000502:physiology*; D010496:Pericardium / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism / Q000502:physiology*
chemical_list: D004041:Dietary Fats; D007328:Insulin; D051899:Smad2 Protein; C422405:activin A; D028341:Activins; D051057:Proto-Oncogene Proteins c-akt; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium