title: Endocardium Contributes to Cardiac Fat.
abstract: BACKGROUND
  Unraveling the developmental origin of cardiac fat could offer important implications for the treatment of cardiovascular disease. The recent identification of the mesothelial source of epicardial fat tissues reveals a heterogeneous origin of adipocytes in the adult heart. However, the developmental origin of adipocytes inside the heart, namely intramyocardial adipocytes, remains largely unknown.
  
  
  OBJECTIVE
  To trace the developmental origin of intramyocardial adipocytes.
  
  
  RESULTS
  In this study, we identified that the majority of intramyocardial adipocytes were restricted to myocardial regions in close proximity to the endocardium. Using a genetic lineage tracing model of endocardial cells, we found that Nfatc1(+) endocardial cells contributed to a substantial number of intramyocardial adipocytes. Despite the capability of the endocardium to generate coronary vascular endothelial cells surrounding the intramyocardial adipocytes, results from our lineage tracing analyses showed that intramyocardial adipocytes were not derived from coronary vessels. Nevertheless, the endocardium of the postnatal heart did not contribute to intramyocardial adipocytes during homeostasis or after myocardial infarction.
  
  
  CONCLUSIONS
  Our in vivo fate-mapping studies demonstrated that the developing endocardium, but not the vascular endothelial cells, gives rise to intramyocardial adipocytes in the adult heart.
authors.affiliation: From the Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China (H.Z., W.P., Q.L., L.H., X.H., X.T., L.Z., B.Z.); Department of Cardiovascular Surgery, Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China (Y.N., S.H.); Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China (K.O.L.); Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai China (B.Z.); and ShanghaiTech University, Shanghai, China (B.Z.).
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: From the Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China (H.Z., W.P., Q.L., L.H., X.H., X.T., L.Z., B.Z.); Department of Cardiovascular Surgery, Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China (Y.N., S.H.); Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China (K.O.L.); Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai China (B.Z.); and ShanghaiTech University, Shanghai, China (B.Z.).
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Pu
authors.affiliation: From the Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China (H.Z., W.P., Q.L., L.H., X.H., X.T., L.Z., B.Z.); Department of Cardiovascular Surgery, Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China (Y.N., S.H.); Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China (K.O.L.); Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai China (B.Z.); and ShanghaiTech University, Shanghai, China (B.Z.).
authors.forename: Qiaozhen
authors.initials: Q
authors.lastname: Liu
authors.affiliation: From the Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China (H.Z., W.P., Q.L., L.H., X.H., X.T., L.Z., B.Z.); Department of Cardiovascular Surgery, Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China (Y.N., S.H.); Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China (K.O.L.); Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai China (B.Z.); and ShanghaiTech University, Shanghai, China (B.Z.).
authors.forename: Lingjuan
authors.initials: L
authors.lastname: He
authors.affiliation: From the Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China (H.Z., W.P., Q.L., L.H., X.H., X.T., L.Z., B.Z.); Department of Cardiovascular Surgery, Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China (Y.N., S.H.); Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China (K.O.L.); Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai China (B.Z.); and ShanghaiTech University, Shanghai, China (B.Z.).
authors.forename: Xiuzhen
authors.initials: X
authors.lastname: Huang
authors.affiliation: From the Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China (H.Z., W.P., Q.L., L.H., X.H., X.T., L.Z., B.Z.); Department of Cardiovascular Surgery, Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China (Y.N., S.H.); Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China (K.O.L.); Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai China (B.Z.); and ShanghaiTech University, Shanghai, China (B.Z.).
authors.forename: Xueying
authors.initials: X
authors.lastname: Tian
authors.affiliation: From the Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China (H.Z., W.P., Q.L., L.H., X.H., X.T., L.Z., B.Z.); Department of Cardiovascular Surgery, Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China (Y.N., S.H.); Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China (K.O.L.); Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai China (B.Z.); and ShanghaiTech University, Shanghai, China (B.Z.).
authors.forename: Libo
authors.initials: L
authors.lastname: Zhang
authors.affiliation: From the Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China (H.Z., W.P., Q.L., L.H., X.H., X.T., L.Z., B.Z.); Department of Cardiovascular Surgery, Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China (Y.N., S.H.); Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China (K.O.L.); Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai China (B.Z.); and ShanghaiTech University, Shanghai, China (B.Z.).
authors.forename: Yu
authors.initials: Y
authors.lastname: Nie
authors.affiliation: From the Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China (H.Z., W.P., Q.L., L.H., X.H., X.T., L.Z., B.Z.); Department of Cardiovascular Surgery, Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China (Y.N., S.H.); Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China (K.O.L.); Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai China (B.Z.); and ShanghaiTech University, Shanghai, China (B.Z.).
authors.forename: Shengshou
authors.initials: S
authors.lastname: Hu
authors.affiliation: From the Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China (H.Z., W.P., Q.L., L.H., X.H., X.T., L.Z., B.Z.); Department of Cardiovascular Surgery, Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China (Y.N., S.H.); Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China (K.O.L.); Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai China (B.Z.); and ShanghaiTech University, Shanghai, China (B.Z.).
authors.forename: Kathy O
authors.initials: KO
authors.lastname: Lui
authors.affiliation: From the Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China (H.Z., W.P., Q.L., L.H., X.H., X.T., L.Z., B.Z.); Department of Cardiovascular Surgery, Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China (Y.N., S.H.); Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China (K.O.L.); Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai China (B.Z.); and ShanghaiTech University, Shanghai, China (B.Z.). zhoubin@sibs.ac.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage; D004195:Disease Models, Animal; D004699:Endocardium / Q000166:cytology* / Q000378:metabolism; D005318:Fetal Heart / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006706:Homeostasis; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010641:Phenotype
chemical_list: D015415:Biomarkers; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse
keywords: adipocytes; endocardium; endothelial cells; homeostasis; pericardium