International Medical Center, Geriatric Department, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
Department of Cardiovascular Medicine, Changsha Central Hospital, Changsha, Hunan 410001, P.R. China.
Mol Med Rep. 2019 Oct;20(4):3285-3291. doi: 10.3892/mmr.2019.10557. Epub 2019 Aug 6.
Niacin is currently the most effective drug that increases HDL‑C levels. Apolipoprotein M (ApoM) in humans is mainly found in plasma high‑density lipoprotein (HDL). Little is known about the role played by niacin in ApoM expression. In this study, the effects of niacin on ApoM expression were assessed as well as the associated mechanism. Human liver cancer cell line HepG2 was treated with niacin alone or with liver X receptor‑α (LXRα) inhibitor at multiple concentrations. The mRNA and protein expression of ApoM were assessed by qRT‑PCR and western blotting. Specific LXRα shRNA was transfected into HepG2 cells to further evaluate the regulatory effects of LXRα on ApoM. An in vivo model was also established to investigate the LXRα inhibitor on the mouse ApoM levels. The comparisons among groups were evaluated using one‑way ANOVA and Student‑Newman‑Keuls test. It was revealed that in HepG2 cells, niacin dose‑dependently increased ApoM gene and protein expression levels. Niacin‑induced upregulation of ApoM was attenuated by an LXRα inhibitor or LXRα shRNA, indicating that LXRα mediated this effect. Moreover, niacin treatment resulted in increased LXRα mRNA levels, in vivo and in vitro; niacin treatment resulted in increased ApoM gene and protein expression levels in mice. In conclusion, niacin upregulates ApoM expression by increasing LXRα expression in vivo and in vitro.
烟酸是目前升高 HDL-C 水平最有效的药物。载脂蛋白 M(ApoM)在人类体内主要存在于血浆高密度脂蛋白(HDL)中。目前对于烟酸在 ApoM 表达中的作用知之甚少。在本研究中,评估了烟酸对 ApoM 表达的影响及其相关机制。用人肝癌细胞系 HepG2 分别用烟酸或肝 X 受体-α(LXRα)抑制剂在多个浓度处理。通过 qRT-PCR 和 Western blot 评估 ApoM 的 mRNA 和蛋白表达。将特异性 LXRα shRNA 转染到 HepG2 细胞中,进一步评估 LXRα对 ApoM 的调节作用。还建立了体内模型,以研究 LXRα 抑制剂对小鼠 ApoM 水平的影响。采用单因素方差分析和 Student-Newman-Keuls 检验比较组间差异。结果显示,在 HepG2 细胞中,烟酸呈剂量依赖性地增加 ApoM 基因和蛋白表达水平。LXRα 抑制剂或 LXRα shRNA 减弱了烟酸诱导的 ApoM 上调,表明 LXRα 介导了这种作用。此外,烟酸处理导致 LXRα mRNA 水平在体内和体外均增加;烟酸处理导致小鼠 ApoM 基因和蛋白表达水平增加。总之,烟酸通过增加体内和体外的 LXRα 表达来上调 ApoM 表达。