Isoquercitrin activates the AMP-activated protein kinase (AMPK) signal pathway in rat H4IIE cells.
BACKGROUND
Isoquercitrin, a flavonoid compound that is widely distributed in medicinal and dietary plants, possesses many biological activities, including inhibition of adipocyte differentiation. In this study, we investigated the effect of isoquercitrin on lipid accumulation and its molecular mechanisms in rat hepatoma H4IIE cells.


METHODS
To investigate the effect of isoquercitrin on lipid accumulation, H4IIE cells were induced by FFA and the total lipid levels were detected by Oil Red O staining. Furthermore, The protein levels of AMPK and acetyl-CoA carboxylase (ACC), the gene expressions of transcriptional factor, lipogenic genes, and adiponectin receptor 1 (AdipoR1) were analyzed by Western blotting and quantitative real-time PCR. To further confirm the pathway of isoquercitrin-mediated hepatic lipid metabolism, H4IIE cells were treated with an AMPK inhibitor and AdipoR1 siRNA.


RESULTS
Isoquercitrin significantly enhances AMPK phosphorylation, downregulates sterol regulatory element binding protein transcription factor 1 (SREBP-1) and fatty acid synthase (FAS) gene expressions. Pretreatment with AMPK inhibitor, significantly decreased the AMPK phosphorylation and increased FAS expression stimulated by isoquercitrin. Isoquercitrin might also upregulate the expression of AdipoR1 dose-dependently via AMPK in the presence of an AMPK inhibitor and AdipoR1 siRNA.


CONCLUSIONS
Isoquercitrin appears to regulate AMPK activation, thereby enhancing AdipoR1 expression, suppressing SREBP-1 and FAS expressions, and resulting in the regulation of lipid accumulation. These results suggest that isoquercitrin is a novel dietary compound that can be potentially be used to prevent lipid metabolic disorder and nonalcoholic fatty liver disease.
Jingxin
J
Zhou
Hisae
H
Yoshitomi
Beijing University of Chinese Medicine, 11 North 3rd-ring East Road, Beijing, Chaoyang District 100029, People's Republic of China. thliu@vip.163.com.
Tonghua
T
Liu
Boxin
B
Zhou
Wen
W
Sun
Lingling
L
Qin
Xiangyu
X
Guo
Liansha
L
Huang
Lili
L
Wu
Ming
M
Gao
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D015536:Down-Regulation; D064429:Fatty Acid Synthases / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D010945:Plants, Edible / Q000737:chemistry; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D054419:Receptors, Adiponectin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism
D010936:Plant Extracts; D054419:Receptors, Adiponectin; D051780:Sterol Regulatory Element Binding Protein 1; C504339:adiponectin receptor 1, rat; C016527:isoquercitrin; D011794:Quercetin; D064429:Fatty Acid Synthases; D055372:AMP-Activated Protein Kinases