Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Gut and Liver Research Center, Non-communicable Disease Institute, Mazandaran University of Medical Sciences, Sari, Iran.
Cell Biochem Biophys. 2022 Sep;80(3):537-545. doi: 10.1007/s12013-022-01077-1. Epub 2022 Jun 15.
Metformin improves lipid profile, however, combination therapy is developing to increase its effectiveness and reduce the deleterious effects of metformin. Chlorogenic acid (CGA) has exhibited lipid-lowering effects. This study aimed to investigate the combined effect of metformin and CGA on lipid accumulation, as well as to elucidate the engaged mechanism in HepG2 cells. To find the non-lethal doses of metformin and CGA, MTT assay was performed. High Glucose (HG) at 33 mM was used to induce lipogenesis in HepG2 cells. Following treatment with different concentrations of metformin and CGA, total lipid content (Oil Red O-staining), triglyceride level, the genes expression of SREBP-1c and FAS, and phosphorylation of AMPK and ACC were measured. Both Metformin and CGA decreased HG-induced lipid accumulation individually, by decreasing total lipid content and triglyceride level. The lowest effective doses of metformin and CGA were 0.25 mM and 5 μM, respectively, which significantly reduced SREBP-1c and FAS genes expression. The combination of these concentrations reinforced these effects. The phosphorylation of AMPK and ACC were more increased by metformin in combination with CGA than both individually. Our findings suggest that CGA synergistically enhances metformin lipid reducing action via the regulating of involved factors in fatty acid synthesis. Therefore, co-administration of metformin with CGA may have further medical value in treating lipid metabolism disorders.
二甲双胍可改善血脂水平，但联合治疗正在开发中，以提高其疗效并降低二甲双胍的有害作用。绿原酸（CGA）已表现出降低血脂的作用。本研究旨在研究二甲双胍和 CGA 联合对脂质积累的影响，并阐明在 HepG2 细胞中涉及的机制。为了找到二甲双胍和 CGA 的非致死剂量，进行了 MTT 测定。使用 33mM 的高葡萄糖（HG）诱导 HepG2 细胞脂肪生成。用不同浓度的二甲双胍和 CGA 处理后，测量总脂质含量（油红 O 染色）、甘油三酯水平、SREBP-1c 和 FAS 的基因表达以及 AMPK 和 ACC 的磷酸化。二甲双胍和 CGA 均可单独降低 HG 诱导的脂质积累，减少总脂质含量和甘油三酯水平。二甲双胍和 CGA 的最低有效剂量分别为 0.25mM 和 5μM，可显著降低 SREBP-1c 和 FAS 基因表达。这些浓度的组合增强了这些作用。与单独使用相比，二甲双胍与 CGA 联合使用时，AMPK 和 ACC 的磷酸化增加更多。我们的研究结果表明，CGA 通过调节脂肪酸合成中涉及的因素与二甲双胍协同增强其降低脂质的作用。因此，二甲双胍与 CGA 联合给药可能在治疗脂质代谢紊乱方面具有更大的医学价值。
