Obesity Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances via MAPK Pathway Activation in Intervertebral Disk Degeneration
Obesity Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances via MAPK Pathway Activation in Intervertebral Disk Degeneration
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肥胖通过 MAPK 通路激活介导椎间盘退变中的细胞凋亡和细胞外基质代谢失衡
DOI：
10.3389/fphys.2019.01284
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发表时间：
2019-10
影响因子：
4
通讯作者：
Zhao Fengdong
中科院分区：
文献类型：
--
作者：
Zhang Xuyang;Chen Jian;Huang Bao;Wang Jiasheng;Shan Zhi;Liu Junhui;Chen Yilei;Li Shengyun;Fan Shunwu;Zhao Fengdong
肥胖可能通过非机械方式促进椎间盘退变（IDD），即影响游离脂肪酸的水平，从而损害细胞代谢。本研究旨在确定肥胖相关 IDD 中独立于机械负荷的代谢因素。在临床研究中，我们回顾性评估了128名志愿者（73名男性，55名女性，年龄29-88岁），并将他们的椎间盘退变程度与体重、BMI和血脂水平等肥胖相关因素进行比较。临床上，IDD组表现出年龄、BMI和血清甘油三酯的增加。即使在校正 BMI 和年龄后，甘油三酯仍然是 IDD 的一个重要危险因素 (P = 0.007)。在肥胖动物模型中，给大鼠喂食高脂饮食（HFD），以研究其对椎间盘代谢和细胞凋亡的影响。 HFD大鼠的血清脂质水平显着升高，包括甘油三酯和非酯化脂肪酸，并且合成代谢标志物显着降低，椎间盘分解代谢和细胞凋亡增加。最后，用脂肪酸（棕榈酸，PA）在体外刺激大鼠髓核（NP）细胞，以测量其对细胞代谢和细胞凋亡的影响。细胞培养研究表明，暴露于 PA 的 NP 细胞显示出因 caspase 3、7、9 和 PARP 激活而导致的细胞凋亡增加，这主要是通过 MAPK 信号通路，尤其是 ERK 通路。总之，高甘油三酯血症可导致 IDD，与年龄和 BMI 无关。高甘油三酯血症似乎主要通过 ERK 途径介导椎间盘细胞凋亡和基质分解代谢。
Obesity may promote intervertebral disc degeneration (IDD) by non-mechanical means, by influencing levels of free fatty acids which could impair cell metabolism. This study aims to establish metabolic factors in obesity-related IDD independent of mechanical loading. In clinical study, we retrospectively reviewed 128 volunteers (73 males, 55 females, aged 29–88 years) and compared their grades of disk degeneration with obesity-related factors such as body weight, BMI, and serum lipid levels. Clinically, the IDD group showed increased age, BMI and serum triglyceride. Triglyceride was a significant risk factor for IDD even after correction for BMI and age (P = 0.007). In obesity animal model, rats were fed a high-fat diet (HFD) in order to study its effects on disk metabolism and apoptosis. HFD rats had significantly higher serum levels of lipids, including triglyceride and non-esterified fatty acid, and showed significantly decreased markers of anabolism, increased catabolism and apoptosis in disk. Finally, rat nucleus pulposus (NP) cells were stimulated in vitro with a fatty acid (palmitic acid, PA) to gauge its effects on cell metabolism and apoptosis. Cell culture studies showed that NP cells exposed to PA showed increased apoptosis for activation of caspase 3, 7, 9, and PARP, which was primarily via the MAPK signal pathway, especially ERK pathway. In conclusion, hypertriglyceridemia can lead to IDD, independently of age and BMI. Hypertriglyceridemia appears to mediate disk cell apoptosis and matrix catabolism primarily via the ERK pathway.
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