title: Pronuciferine and nuciferine inhibit lipogenesis in 3T3-L1 adipocytes by activating the AMPK signaling pathway.
abstract: OBJECTIVE
  Nelumbo nucifera (Gaertn.) leaves are used widely in modulating obesity in traditional Chinese medicine. Our previous work demonstrated that aporphine alkaloids from it increased the glucose consumption in mature 3T3-L1 adipocytes. However, the underlying mechanisms of this increase remain unclear. Here we investigated the modulating effects of pronuciferine and nuciferine on lipogenesis and glucose uptake in insulin resistant 3T3-L1 adipocytes in vitro.
  
  
  METHODS
  Insulin resistant 3T3-L1 mature adipocytes were induced with dexamethasone, 3-isobutyl-methylxanthine and insulin. The lipid droplets and the intracellular triglyceride contents in mature adipocytes were detected by Oil red O staining and colorimetry respectively. The glucose uptake was measured with a fluorescent deoxyglucose analog (2-NBDG). The glucose transporter type 4 (GLUT-4) expression was measured by fluorescent-immunohistochemistry and the activation of 5'-AMP-activated protein kinase (AMPK) was detected by its alpha subunit phosphorylation.
  
  
  RESULTS
  Both nuciferine and pronuciferine treatments significantly decreased the lipid droplets and the intracellular triglyceride contents but increased the glucose uptake in the insulin resistant 3T3-L1 adipocytes. Furthermore, both pronuciferine and nuciferine showed the ability to up-regulate the expression of GLUT4, triggering the phosphorylation of AMPK in mature 3T3-L1 adipocytes, although pronuciferine exhibited a more powerful effect compared to nuciferine.
  
  
  CONCLUSIONS
  In summary, all the results demonstrate that pronuciferine and nuciferine ameliorate the glucose and lipid metabolism in insulin-resistant 3T3-L1 adipocytes, which might be due to the activation of the AMPK signaling pathway.
authors.affiliation: Center of Mitochondria and Healthy Aging, School of Life Sciences, Yantai University, Yantai 264005, China.
authors.forename: Chengjun
authors.initials: C
authors.lastname: Ma
authors.affiliation: Center of Mitochondria and Healthy Aging, School of Life Sciences, Yantai University, Yantai 264005, China; Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xi'ning 810001, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xi'ning 810001, China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: He
authors.affiliation: Center of Mitochondria and Healthy Aging, School of Life Sciences, Yantai University, Yantai 264005, China; Key Laboratory of Molecular Pharmacology and Drug Evaluation (Ministry of Education of China), School of Pharmacy, Yantai University, Yantai 264005, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.affiliation: School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Xiangquan
authors.initials: X
authors.lastname: Mi
authors.affiliation: Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xi'ning 810001, China.
authors.forename: Honglun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Center of Mitochondria and Healthy Aging, School of Life Sciences, Yantai University, Yantai 264005, China. Electronic address: skywzh@ytu.edu.cn.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Wang
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D001060:Aporphines / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D066292:Lipid Droplets / Q000378:metabolism; D050155:Lipogenesis / Q000187:drug effects*; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects*; D013141:Spiro Compounds / Q000494:pharmacology*
chemical_list: D019440:Anti-Obesity Agents; D001060:Aporphines; D051275:Glucose Transporter Type 4; C495693:Slc2a4 protein, mouse; D013141:Spiro Compounds; C514305:pronuciferine; D055372:AMP-Activated Protein Kinases; D005947:Glucose; C008692:nuciferine
keywords: 3T3-L1 adipocytes; AMPK; Lipogenesis; Nuciferine; Pronuciferine