title: A promising culture model for analyzing the interaction between adipose tissue and cardiomyocytes.
abstract: The heart has epicardial adipose tissue that produces adipokines and mesenchymal stem cells. Systemic adipose tissue is involved in the pathophysiology of obesity-related heart diseases. However, the method for analyzing the direct interaction between adipose tissue and cardiomyocytes has not been established. Here we show the novel model, using collagen gel coculture of adipose tissue fragments (ATFs) and HL-1 cardiomyocytes, and electron microscopy, immunohistochemistry, real-time RT-PCR, and ELISA. HL-1 cells formed a stratified layer on ATF-nonembedded gel, whereas they formed almost a monolayer on ATF-embedded gel. ATFs promoted the apoptosis, lipid accumulation, and fatty acid transport protein (FATP) expression of FATP4 and CD36 in HL-1 cells, whereas ATFs inhibited the growth and mRNA expression of myosin, troponin T, and atrial natriuretic peptide. Treatment of leptin (100 ng/ml) and adiponectin (10 μg/ml) neither replicated nor abolished the ATF-induced morphology of HL-1 cells, whereas that of FATP4 and CD36 antibodies (25 μg/ml) never abolished it. HL-1 cells prohibited the development of CD44+/CD105+ mesenchymal stem cell-like cells and lipid-laden preadipocytes from ATFs. HL-1 cells increased the production of adiponectin in ATFs, whereas they decreased that of leptin. The data indicate that our model actively creates adipose tissue-HL-1 cardiomyocyte interaction, suggesting first that ATFs may be related to the lipotoxiciy of HL-1 cells via unknown factors plus FATP4 and CD36 and second that HL-1 cells may help to retain the static state of ATFs, affecting adipokine secretion. Our model will serve to study adipose tissue-cardiomyocyte interaction and mechanisms of obesity-related lipotoxicity and heart diseases.
authors.affiliation: Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Nabeshima 5-1-1, Saga 849-8501, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Anan
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Uchihashi
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Aoki
authors.forename: Aki
authors.initials: A
authors.lastname: Matsunobu
authors.forename: Akifumi
authors.initials: A
authors.lastname: Ootani
authors.forename: Koichi
authors.initials: K
authors.lastname: Node
authors.forename: Shuji
authors.initials: S
authors.lastname: Toda
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D050612:Fatty Acid Transport Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008854:Microscopy, Electron; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D009218:Myosins / Q000235:genetics / Q000378:metabolism; D041681:NIH 3T3 Cells; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020107:Troponin T / Q000235:genetics / Q000378:metabolism
chemical_list: D050612:Fatty Acid Transport Proteins; D020107:Troponin T; D009320:Atrial Natriuretic Factor; D009218:Myosins