Hypolipogenic Effect of Shikimic Acid Via Inhibition of MID1IP1 and Phosphorylation of AMPK/ACC

• Published in: International journal of molecular sciences Vol. 20; no. 3; p. 582
• Main Authors: Kim, Moon Joon, Sim, Deok Yong, Lee, Hye Min, Lee, Hyo-Jung, Kim, Sung-Hoon
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.01.2019; MDPI
• Subjects: 3T3-L1; Adipocytes; AMP-activated protein kinase; AMPK; Analgesics; Antioxidants; Coenzyme A; Cytotoxicity; Diabetes mellitus; Energy charge; Fatty acids; Fatty liver; Food cans; Hepatocellular carcinoma; hepatocellular carcinoma (HCC); Illicium verum; Inflammation; Kinases; Lipids; lipogenesis; Liver; Liver cancer; Liver diseases; Metabolism; MID1IP1; Oseltamivir; Oxidation; Phosphorylation; Plasmids; Proteins; Seeds; Shikimic acid; Transcription; Triglycerides; St Louis Missouri; United States > US; AMPK; hepatocellular carcinoma (HCC); lipogenesis; MID1IP1; 3T3-L1; shikimic acid
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20030582

Although shikimic acid from 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.