Department of Spine Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Department of Orthopaedic Trauma, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Biol Direct. 2023 Nov 14;18(1):75. doi: 10.1186/s13062-023-00436-z.
Ligamentum flavum (LF) hypertrophy is the main cause of lumbar spinal canal stenosis (LSCS). Previous studies have shown that LF hypertrophy tissue exhibits abnormal lipid accumulation, but the regulatory mechanism remains unclear. The objective of this study was to explore the function and potential mechanism of ACSM5 in LF lipid accumulation.
To assess the ACSM5 expression levels, lipid accumulation and triglyceride (TG) level in LF hypertrophy and normal tissue, we utilized RT-qPCR, western blot, oil red O staining, and TG assay kit. The pearson correlation coefficient assay was used to analyze the correlation between ACSM5 levels and lipid accumulation or TG levels in LF hypertrophy tissue. The role of ACSM5 in free fatty acids (FFA)-induced lipid accumulation in LF cells was assessed in vitro, and the role of ACSM5 in LF hypertrophy in mice was verified in vivo. To investigate the underlying mechanisms of ACSM5 regulating lipid accumulation in LF, we conducted the mRNA sequencing, bioinformatics analysis, and rescue experiments.
In this study, we found that ACSM5, which was significantly down-regulated in LF tissues, correlated with lipid accumulation. In vitro cell experiments demonstrated that overexpression of ACSM5 significantly inhibited FFA-induced lipid accumulation and fibrosis in LF cells. In vivo animal experiments further confirmed that overexpression of ACSM5 inhibited LF thickening, lipid accumulation, and fibrosis. Mechanistically, ACSM5 inhibited lipid accumulation of LF cells by inhibiting FABP4-mediated PPARγ signaling pathway, thereby improving hypertrophy and fibrosis of LF.
our findings elucidated the important role of ACSM5 in the regulation of LF lipid accumulation and provide insight into potential therapeutic interventions for the treatment of LF hypertrophy. This study further suggested that therapeutic strategies targeting lipid deposition may be an effective potential approach to treat LF hypertrophy-induced LSCS.
黄韧带肥厚（LF）是腰椎管狭窄症（LSCS）的主要原因。先前的研究表明，LF 肥厚组织表现出异常的脂质积累，但调节机制尚不清楚。本研究旨在探讨 ACSM5 在 LF 脂质积累中的功能和潜在机制。
为了评估 ACSM5 的表达水平、LF 肥厚和正常组织中的脂质积累和三酰甘油（TG）水平，我们利用 RT-qPCR、western blot、油红 O 染色和 TG 测定试剂盒进行检测。采用皮尔逊相关系数分析方法分析 ACSM5 水平与 LF 肥厚组织中脂质积累或 TG 水平之间的相关性。在体外评估 ACSM5 在游离脂肪酸（FFA）诱导的 LF 细胞脂质积累中的作用，并在体内验证 ACSM5 在小鼠 LF 肥厚中的作用。为了研究 ACSM5 调节 LF 脂质积累的潜在机制，我们进行了 mRNA 测序、生物信息学分析和挽救实验。
在这项研究中，我们发现 ACSM5 在 LF 组织中显著下调，与脂质积累相关。体外细胞实验表明，ACSM5 的过表达显著抑制了 FFA 诱导的 LF 细胞脂质积累和纤维化。体内动物实验进一步证实，ACSM5 的过表达抑制了 LF 的增厚、脂质积累和纤维化。机制上，ACSM5 通过抑制 FABP4 介导的 PPARγ 信号通路抑制 LF 细胞的脂质积累，从而改善 LF 的肥厚和纤维化。
我们的研究结果阐明了 ACSM5 在调节 LF 脂质积累中的重要作用，并为 LF 肥厚的治疗提供了潜在的治疗干预靶点。本研究进一步表明，针对脂质沉积的治疗策略可能是治疗 LF 肥厚引起的 LSCS 的有效潜在方法。
