title: Extracts from Aralia elata (Miq) Seem alleviate hepatosteatosis via improving hepatic insulin sensitivity.
abstract: BACKGROUND
  Non-alcoholic fatty liver disease (NAFLD) is a common liver disease that is strongly associated with obesity and dysregulation of insulin in the liver. However, currently no pharmacological agents have been established for the treatment of NAFLD. In this regard, we sought to evaluate the anti-NAFLD effects of Aralia elata (Miq) Seem (AE) extract and its ability to inhibit hepatic lipid accumulation and modulate cellular signaling in a high fat diet (HFD)-induced obese mouse model.
  
  
  METHODS
  A model of hepatic steatosis in the HepG2 cells was induced by oleic acid. Intracellular lipid droplets were detected by Oil-Red-O staining, and the expression of sterol regulatory element-binding protein 1(SREBP-1), Fatty acid synthase (FAS), Acetyl-CoA carboxylase (ACC) 1 and 2, Peroxisome proliferator activated receptor-α (PPARα), and carnitine palmitoyl transferase 1(CPT-1) was analyzed by real time reverse transcription-Polymerase chain reaction (qRT-PCR). And glucose consumption was measured with commercial kit. Furthermore, Male C57BL/6 J mice were fed with HFD to induce NAFLD. Groups of mice were given plant extracts orally at 100 and 300 mg/kg at daily for 4 weeks. After 3 weeks of AE extract treatment, we performed oral glucose tolerance test (OGTT). Liver tissue was procured for histological examination, Phosphoinositide 3-kinase (PI3K) and Protein kinase B (PKB/Akt) activity.
  
  
  RESULTS
  In the present study, AE extract was shown to reduce hepatic lipid accumulation and significantly downregulate the level of lipogenic genes and upregulate the expression of lipolysis genes in HepG2 cells. And also, AE extract significantly increased the glucose consumption, indicating that AE extract improved insulin resistance. Subsequently, we confirmed the inhibitory activity of AE extract on NAFLD, in vivo. Treatment with AE extract significantly decreased body weight and the fasting glucose level, alleviated hyperinsulinism and hyperlipidemia, and reduced glucose levels, as determined by OGTT. Additionally, AE extract decreased PI3K and Akt activity.
  
  
  CONCLUSIONS
  Our results suggest that treatment with AE extract ameliorated NAFLD by inhibiting insulin resistance through activation of the Akt/GLUT4 pathway.
authors.affiliation: Department of Agrofood Resources, National Academy of Agricultural Science, RDA, Wanju-Gun, Jeollabuk-do, 565-851, Republic of Korea. kah366@korea.kr.
authors.forename: Kyung-A
authors.initials: KA
authors.lastname: Hwang
authors.affiliation: Department of Agrofood Resources, National Academy of Agricultural Science, RDA, Wanju-Gun, Jeollabuk-do, 565-851, Republic of Korea. yjhwang1022@korea.kr.
authors.forename: Yu-Jin
authors.initials: YJ
authors.lastname: Hwang
authors.affiliation: Department of Agrofood Resources, National Academy of Agricultural Science, RDA, Wanju-Gun, Jeollabuk-do, 565-851, Republic of Korea. ysamang@skku.edu.
authors.forename: Ga Ram
authors.initials: GR
authors.lastname: Kim
authors.affiliation: Department of Agrofood Resources, National Academy of Agricultural Science, RDA, Wanju-Gun, Jeollabuk-do, 565-851, Republic of Korea. swany@korea.kr.
authors.forename: Jeong-Sook
authors.initials: JS
authors.lastname: Choe
mesh_terms: D000818:Animals; D027983:Aralia / Q000737:chemistry*; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D007328:Insulin; D047493:PPAR alpha; D010936:Plant Extracts; D051780:Sterol Regulatory Element Binding Protein 1; D002334:Carnitine O-Palmitoyltransferase; D019869:Phosphatidylinositol 3-Kinases