Abstract
Although shikimic acid from Illicium verum has antioxidant, antibacterial, anti-inflammatory, and analgesic effects, the effect of shikimic acid on lipogenesis has not yet been explored. Thus, in the present study, hypolipogenic mechanism of shikimic acid was examined in HepG2, Huh7 and 3T3-L1 adipocyte cells. Shikimic acid showed weak cytotoxicity in HepG2, Huh7 and 3T3-L1 cells, but suppressed lipid accumulation in HepG2, Huh7 and 3T3-L1 cells by Oil Red O staining. Also, shikimic acid attenuated the mRNA expression of de novo lipogenesis related genes such as FAS, SREBP-1c, and LXR-α in HepG2 cells by RT-PCR analysis and suppressed the protein expression of SREBP-1c and LXR-α in HepG2 and 3T3-L1 cells. It should be noted that shikimic acid activated phosphorylation of AMP-activated protein kinase (AMPK)/Aacetyl-coenzyme A carboxylase (ACC) and reduced the expression of MID1 Interacting Protein 1 (MID1IP1) in HepG2, Huh7 and 3T3-L1 cells. Conversely, depletion of MID1IP1 activated phosphorylation of AMPK, while overexpression of MID1IP1 suppressed phosphorylation of AMPK in HepG2 cells. However, AMPK inhibitor compound c did not affect the expression of MID1IP1, indicating MID1IP1 as an upstream of AMPK. Taken together, our findings suggest that shikimic acid has hypolipogenic effect in HepG2 and 3T3-L1 cells via phosphorylation of AMPK/ACC and inhibition of MID1IP1 as a potent candidate for prevention or treatment of fatty liver and hyperlipidemia.
Highlights
Fatty liver disease is caused by excessive fat accumulation, leading to progressive liver fibrosis and cirrhosis with features of metabolic syndrome including insulin resistance [1,2]
It is well documented that De Novo lipogenesis (DNL) can induce hepatic steatosis and/or hypertriglyceridemia, and cause steatohepatitis by saturated fatty acids including palmitate [6]
DNL is regulated mainly by two key transcription factors such as sterol regulatory element-binding protein 1c (SREBP1c), which is activated by insulin and liver X receptor α (LXR-α), and carbohydrate regulatory element-binding protein (ChREBP) [7,8]
Summary
Fatty liver disease is caused by excessive fat accumulation, leading to progressive liver fibrosis and cirrhosis with features of metabolic syndrome including insulin resistance [1,2]. Excessive intake of alcohol or fatty food can induce alcoholic or nonalcoholic fatty liver diseases (NAFLD) [3] by promoting de novo fatty acid synthesis through downregulation of AMP-activated protein kinase (AMPK), an important hepatic transcriptional regulator, and its downstream acetyl CoA carboxylase (ACC) [4,5]. Kim et al [10] reported that MID1IP1 regulates and binds to acetyl-CoA carboxylase (ACC), the first committed enzyme in fatty acid (FA) synthesis, and induces. Claimed that that MID1IP1 regulates ligand glucose, resulting in triglyceride accumulation liver. In the present study, hypolipogenic effects, its hypolipogenic mechanism has never been reported. In the present study, hypolipogenic mechanism of shikimic acid was elucidated in HepG2 and Huh hepatocellular carcinoma HCC cells
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