CCN5 knockout mice exhibit lipotoxic cardiomyopathy with mild obesity and diabetes

Jihwa Kim, Sanghyun Joo, Gwang Hyeon Eom, Seung Hoon Lee, Min Ah Lee, Miyoung Lee, Ki Woo Kim, Do Han Kim, Hyun Kook, Tae Hwan Kwak, Woo Jin Park

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Obesity is associated with various human disorders, such as type 2 diabetes, cardiovascular diseases, hypertension, and cancers. In this study, we observed that knockout (KO) of CCN5, which encodes a matricellular protein, caused mild obesity in mice. The CCN5 KO mice also exhibited mild diabetes characterized by high fasting glucose levels and impaired insulin and glucose tolerances. Cardiac hypertrophy, ectopic lipid accumulation, and impaired lipid metabolism in hearts were observed in the CCN5 KO mice, as determined using histology, quantitative RT-PCR, and western blotting. Fibrosis was significantly greater in hearts from the CCN5 KO mice both in interstitial and perivascular regions, which was accompanied by higher expression of pro-fibrotic and pro-inflammatory genes. Both systolic and diastolic functions were significantly impaired in hearts from the CCN5 KO mice, as assessed using echocardiography. Taken together, these results indicate that CCN5 KO leads to lipotoxic cardiomyopathy with mild obesity and diabetes in mice.

Original languageEnglish
Article numbere0207228
JournalPloS one
Volume13
Issue number11
DOIs
Publication statusPublished - 2018 Nov

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Kim, J., Joo, S., Eom, G. H., Lee, S. H., Lee, M. A., Lee, M., Kim, K. W., Kim, D. H., Kook, H., Kwak, T. H., & Park, W. J. (2018). CCN5 knockout mice exhibit lipotoxic cardiomyopathy with mild obesity and diabetes. PloS one, 13(11), [e0207228]. https://doi.org/10.1371/journal.pone.0207228