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 journalArticlepeer-review

4 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

Bibliographical note

Funding Information:
This work was supported by a Basic Science Research Program grant (2017R1A2B4007340 to WJP), a Basic Research Laboratory Program grant (2016R1A4A1009895 to HK and WJP), and a Bio & Medical Technology Development Program grant (NRF-2015M3A9E6028951 to WJP) from the National Research Foundation, and the Institute for Basic Science Program grant (IBS-R025-D1 to KDH), funded by the Korean government, and The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NadianBio provided support in the form of salaries for SHL and THK, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.

Publisher Copyright:
© 2018 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

All Science Journal Classification (ASJC) codes

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

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