3-Caffeoyl, 4-dihydrocaffeoylquinic acid from Salicornia herbacea attenuates high glucose-induced hepatic lipogenesis in human HepG2 cells through activation of the liver kinase B1 and silent information regulator T1/AMPK-dependent pathway.
METHODS
Increasing evidence indicates that polyphenols may protect against metabolic disease through activating AMP-activated protein kinase (AMPK). The aims of our study were to provide new data on the molecular mechanism(s) underlying the role of the phenolic compound, 3-caffeoyl, 4-dihydrocaffeoylquinic acid (CDCQ) from Salicornia herbacea, in the prevention of high glucose-induced lipogenesis in human HepG2 cells.


RESULTS
Nile red staining assays were used to demonstrate lipid accumulation in the cells. Expression of sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) gene at the levels of promoter activity, mRNA, and protein was demonstrated using transient transfection assays, quantitative RT-PCR, and Western blot analyses, respectively. We found that CDCQ suppressed high glucose-induced lipid accumulation in HepG2 cells. CDCQ strongly inhibited high glucose-induced FAS expression by modulating SREBP-1c activation. Moreover, the use of both a specific inhibitor and liver kinase B1 (LKB1)-siRNA transfected HepG2 cells showed that CDCQ activated AMPK via silent information regulator T1 (SIRT1) or LKB1 in HepG2 cells.


CONCLUSIONS
These results indicate that CDCQ prevented lipid accumulation by blocking the expression of SREBP-1c and FAS through LKB1/SIRT1 and AMPK activation in HepG2 cells, suggesting that CDCQ plays a potential role in the prevention of lipogenesis by AMPK activation.
Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
Yong
Y
Pil Hwang
Hyung
H
Gyun Kim
Jae Ho
JH
Choi
Minh
M
Truong Do
Thu Phuong
TP
Tran
Hyo Kon
HK
Chun
Young Chul
YC
Chung
Tae Cheon
TC
Jeong
Hye Gwang
HG
Jeong
D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D019663:Chenopodiaceae / Q000737:chemistry*; D002726:Chlorogenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000009:adverse effects*; D056945:Hep G2 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D050155:Lipogenesis / Q000187:drug effects*; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism
C544671:3-caffeoyl-4-dihydrocaffeoylquinic acid; D034741:RNA, Small Interfering; D051780:Sterol Regulatory Element Binding Protein 1; D002726:Chlorogenic Acid; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D005947:Glucose