College of Life Sciences, Gwangju Institute of Science and Technology, Buk-gu, Gwangju, Republic of Korea.
Department of Pharmacology and Medical Research Center for Gene Regulation, Chonnam National University Medical School, Hwasun-gun, Jeollanam-do, Republic of Korea.
PLoS One. 2018 Nov 28;13(11):e0207228. doi: 10.1371/journal.pone.0207228. eCollection 2018.
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.
肥胖与多种人类疾病有关，如 2 型糖尿病、心血管疾病、高血压和癌症。在这项研究中，我们观察到，编码细胞外基质蛋白的 CCN5 基因敲除（KO）导致小鼠出现轻度肥胖。CCN5 KO 小鼠还表现出轻度糖尿病的特征，表现为空腹血糖水平升高，胰岛素和葡萄糖耐量受损。通过组织学、定量 RT-PCR 和 Western blot 分析，观察到 CCN5 KO 小鼠的心脏发生心肌肥厚、异位脂质积累和脂质代谢受损。CCN5 KO 小鼠的心脏间质和血管周围区域的纤维化明显增加，伴有促纤维化和促炎基因的高表达。通过超声心动图评估，CCN5 KO 小鼠的收缩和舒张功能均显著受损。综上所述，这些结果表明 CCN5 KO 导致小鼠出现脂毒性心肌病，伴有轻度肥胖和糖尿病。
