title: Ethanol extract of Pinus koraiensis leaves containing lambertianic acid exerts anti-obesity and hypolipidemic effects by activating adenosine monophosphate-activated protein kinase (AMPK).
abstract: BACKGROUND
  In this study, we investigated the anti-obesity and anti-hyperlipidemic mechanisms of lambertianic acid (LA) isolated from Pinus koraiensis leaves and the ethanol extract of Pinus koraiensis leaves (EPK), both in vitro and in vivo.
  
  
  METHODS
  Differentiated 3T3L-1 cells were treated with EPK (25 or 50 μg/mL) or LA (200 μM) and analyzed by western blotting or RT-PCR. In vitro, lipid accumulation of adipocytes was observed using Oil-Red-O staining and triglyceride analysis. The contribution of AMPK to anti-obesity activity was assessed by siRNA-mediated AMPK knockdown. After AMPK silencing, expression of AMPK was observed by western blotting. To confirm the in vitro activity, an animal study was conducted by administering a normal diet, HFD, and EPK for 6 weeks. Obesity-related physiological parameters and protein levels were measured.
  
  
  RESULTS
  LA induced the expression of p-AMPK and inhibited PPARγ, C/EBP α, adiponectin, FAS, SREBP-1, and HMGCR expression. EPK containing LA significantly decreased lipid accumulation and triglyceride levels in the differentiated 3 T3-L1 cells. EPK treatment suppressed the expression of adipogenic transcription factors, FABP, GPDH, and cholesterol-synthesis-related factors in the differentiated 3 T3-L1 cells. EPK increased the expression of p-AMPK. The effects of EPK were reversed on inhibiting AMPK by using AMPK siRNA and compound C. In vivo analysis showed that body weight gain, serum triglyceride, total cholesterol, LDL cholesterol and AI value in the EPK treatment group were lower than those in the HFD control group. EPK induced the expression of p-AMPK and inhibited PPARγ in liver and adipose tissue.
  
  
  CONCLUSIONS
  Overall, the results suggest that EPK containing LA exerts significant anti-obesity and cholesterol-lowering effects by activating AMPK.
authors: Korea Cancer Preventive Material Development Research Center, College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu 130-701, Seoul, Republic of Korea.
authors: Myoung-Sun
authors: MS
authors: Lee
authors: Korea Cancer Preventive Material Development Research Center, College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu 130-701, Seoul, Republic of Korea.
authors: Sun-Mi
authors: SM
authors: Cho
authors: College of health industry, Eulji University, Yangji-dong, Sujeong-gu, Seongnam-si, 461-713, Republic of Korea.
authors: Min-ho
authors: MH
authors: Lee
authors: Korea Cancer Preventive Material Development Research Center, College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu 130-701, Seoul, Republic of Korea.
authors: Eun-Ok
authors: EO
authors: Lee
authors: Korea Cancer Preventive Material Development Research Center, College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu 130-701, Seoul, Republic of Korea.
authors: Sung-Hoon
authors: SH
authors: Kim
authors: Korea Cancer Preventive Material Development Research Center, College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu 130-701, Seoul, Republic of Korea. strong79@khu.ac.kr.
authors: Hyo-Jeong
authors: HJ
authors: Lee
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017667:Adipocytes / Q000187:drug effects; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002264:Carboxylic Acids / Q000302:isolation & purification / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat; D004789:Enzyme Activation / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009281:Naphthalenes / Q000302:isolation & purification / Q000494:pharmacology*; D028223:Pinus / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000378:metabolism
chemical_list: D019440:Anti-Obesity Agents; D002264:Carboxylic Acids; D008055:Lipids; D009281:Naphthalenes; D010936:Plant Extracts; D014280:Triglycerides; C421442:lambertianic acid; D002784:Cholesterol; D055372:AMP-Activated Protein Kinases