鼠尾草酸通过激活AMPK降低游离脂肪酸诱导的HepG2细胞脂肪积累

doi:10.7506/spkx1002-6630-20190602-002

食品科学 ›› 2020, Vol. 41 ›› Issue (11): 171-178.doi: 10.7506/spkx1002-6630-20190602-002

鼠尾草酸通过激活AMPK降低游离脂肪酸诱导的HepG2细胞脂肪积累

程静，刘莹，刘垚杰，赵江，吉洋琳，刘东，王浩

（天津科技大学食品工程与生物技术学院，天津 300457）

出版日期:2020-06-15 发布日期:2020-06-22
基金资助:
国家自然科学基金青年科学基金项目（31701550）；天津市科技计划项目（17KPHDSF00120）

Carnosic Acid Reduces Free Fatty Acid (FFA)-Induced Lipid Accumulation in HepG2 Cells by Activating Adenosine 5’-Monophosphate Activated Protein Kinase (AMPK)

CHENG Jing, LIU Ying, LIU Yaojie, ZHAO Jiang, JI Yanglin, LIU Dong, WANG Hao

(College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China)

Online:2020-06-15 Published:2020-06-22

摘要/Abstract

摘要： 目的：探究鼠尾草酸对游离脂肪酸（free fatty acids，FFAs）诱导的HepG2细胞脂肪积累的作用机制。方法：采用FFAs（油酸-棕榈酸浓度比2∶1）诱导建立HepG2细胞高脂模型，使用不同浓度的鼠尾草酸（15、20 μmol/L）、FFAs（1 mmol/L）、AMP依赖的蛋白激酶（adenosine 5’-monophosphate activated protein kinase，AMPK）抑制剂（2 μmol/L）处理细胞24 h后，通过测定细胞内脂肪含量、细胞活力、总胆固醇（total cholesterol，TC）和甘油三酯（triglyceride，TG）含量，脂肪代谢相关基因的转录表达水平以及磷酸化腺苷酸活化蛋白激酶的表达水平，研究鼠尾草酸的降脂作用机制。结果：15、20 μmol/L的鼠尾草酸，1 mmol/L的FFAs单独或共同处理细胞24 h对细胞的活力没有显著性影响；与正常组相比FFAs处理细胞24 h，油红O染色结果显示，FFAs能显著增加细胞内的脂肪含量；FFAs能增加细胞内TC、TG含量，增加脂肪合成相关基因的表达水平，降低脂肪分解相关基因的表达水平（P＜0.05）。油红O染色结果显示，与FFAs处理组相比，鼠尾草酸可以降低细胞内的脂肪含量；鼠尾草酸能显著降低TC、TG含量，显著下调脂肪合成相关基因的表达，且使脂肪氧化相关基因的表达水平呈上升趋势，并显著上调磷酸化AMPK的表达量（P＜0.05）。使用AMPK抑制剂共同处理细胞24 h，对细胞的活力没有影响，但可明显逆转鼠尾草酸的降脂作用（P＜0.05）。结论：鼠尾草酸能通过调控脂肪相关基因的转录水平和AMPK磷酸化激酶的表达来改善FFAs诱导的HepG2细胞的脂肪积累。

关键词: 鼠尾草酸, 游离脂肪酸, HepG2细胞, AMP依赖的蛋白激酶

Abstract: Objective: The purpose of this study was to investigate the effect of carnosic?acid on free fatty acid (FFA)-induced lipid accumulation in HepG2 cells. Methods: Lipid accumulation in the cells was induced by a blend of oleic acid and palmitic acid at a molar ratio of 2:1. The cells were treated with the fatty acid blend (1 mmol/L) alone or in combination with different concentrations of carnosic acid (15 and 20 μmol/L) as well as 20 μmol/L carnosic acid plus the adenosine 5’-monophosphate activated protein kinase (AMPK) inhibitor Compound C (2 μmol/L) for 24 h. The intracellular lipid content, cell activity, the contents of triglyceride (TG) and total cholesterol (TC), the mRNA expression of genes associated with lipid metabolism and the protein expression of phosphorylated AMPK (p-AMPK) were detected to evaluate the mechanism of action of carnosic acid in lowering lipid accumulation. Results: The fatty acid blend alone and combined with carnosic acid at the concentration of 15, 20 μmol/L had no effect on cell activity. The results of oil red O staining showed that compared to the normal control group, treatment cells with the FFAs for 24 h significantly increased lipid content inside the cells. Meanwhile, upon treatment with the FFAs, the contents of intracellular TC and TG and the expression of lipid anabolism-related genes were increased, and the expression of lipid catabolism-related genes was decreased (P < 0.05). The results of oil red O staining showed that compared to the FFA-induced model group, carnosic?acid reduced intracellular lipid content. Moreover, carnosic?acid remarkably lowered the contents of TC and TG, down-regulated the expression of lipid synthesis-related genes, and up-regulated the expression of lipid oxidation-related genes and the protein expression of p-AMPK (P < 0.05). The AMPK inhibitor had no effect on cell activity, but significantly reversed the lipid-lowering effect of carnosic acid (P < 0.05). Conclusion: Carnosic acid can reduce FFA-induced lipid accumulation in HepG2 cells by regulating the transcriptional level of lipid metabolism-related genes and the expression of p-AMPK.

Key words: carnosic acid, free fatty acids, HepG2 cells, adenosine 5’-monophosphate activated protein kinase

中图分类号:

TS201.4

程静，刘莹，刘垚杰，赵江，吉洋琳，刘东，王浩. 鼠尾草酸通过激活AMPK降低游离脂肪酸诱导的HepG2细胞脂肪积累[J]. 食品科学, 2020, 41(11): 171-178.

CHENG Jing, LIU Ying, LIU Yaojie, ZHAO Jiang, JI Yanglin, LIU Dong, WANG Hao. Carnosic Acid Reduces Free Fatty Acid (FFA)-Induced Lipid Accumulation in HepG2 Cells by Activating Adenosine 5’-Monophosphate Activated Protein Kinase (AMPK)[J]. FOOD SCIENCE, 2020, 41(11): 171-178.

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鼠尾草酸通过激活AMPK降低游离脂肪酸诱导的HepG2细胞脂肪积累

Carnosic Acid Reduces Free Fatty Acid (FFA)-Induced Lipid Accumulation in HepG2 Cells by Activating Adenosine 5’-Monophosphate Activated Protein Kinase (AMPK)

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