title: Flavonoid ingredients of Ginkgo biloba leaf extract regulate lipid metabolism through Sp1-mediated carnitine palmitoyltranferase 1A up-regulation.
abstract: BACKGROUND
  Lipid accumulation is the primary evidence of non-alcoholic fatty liver disease (NAFLD). Ginkgo biloba extract (GBE) and its flavonoid ingredients (quercetin, kaempferol, and isorhamnetin) could lessen the lipid accumulation associated with up-regulation of the rate-limiting enzyme, carnitine palmitoyltransferase 1A (CPT1A), in the β-oxidation of long-chain fatty acids. In this study, we investigated the mechanisms by which GBE and its flavonoids induced expression of CPT1A.
  
  
  RESULTS
  CPT1A inhibition with RNAi resulted in triglyceride accumulation in HepG2 cells. Through deletion and mutation analysis of CPT1A's promoter combined with electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) experiments, the CPT1A promoter region (-50 to -5 nt) was determined to contain two putative Sp1 binding sites, namely Sp1a and Sp1b, which might act as the GBE regulation response DNA element. Sp1 might be induced to transfer from cytoplasma to nucleus to bind the promoter region of -50 to -5 nt by GBE. The regulatory effects of GBE on CPT1A were also verified on the flavonoid ingredients quercetin, kaempferol, and isorhamnetin.
  
  
  CONCLUSIONS
  Sp1 was crucial in regulating CPT1A expression with GBE and its flavonoid ingredients, and the -50 to -5 nt region of CPT1A promoter played important roles in Sp1 binding.
authors.affiliation: Research Center for Traditional Chinese Medicine and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai, China. ting_life@126.com.|Shanghai-MOST Key Laboratory of Health and Disease Genomics, National Engineering Center for Biochip at Shanghai, Shanghai, China. ting_life@126.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Wei
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, China. f_ashley@163.com.|Shanghai-MOST Key Laboratory of Health and Disease Genomics, National Engineering Center for Biochip at Shanghai, Shanghai, China. f_ashley@163.com.
authors.forename: Fei-fei
authors.initials: FF
authors.lastname: Xiong
authors.affiliation: Research Center for Traditional Chinese Medicine and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai, China. sdwang@wayenbio.com.|Shanghai-MOST Key Laboratory of Health and Disease Genomics, National Engineering Center for Biochip at Shanghai, Shanghai, China. sdwang@wayenbio.com.
authors.forename: Shi-dong
authors.initials: SD
authors.lastname: Wang
authors.affiliation: Shanghai-MOST Key Laboratory of Health and Disease Genomics, National Engineering Center for Biochip at Shanghai, Shanghai, China. wangke8430@163.com.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Research Center for Traditional Chinese Medicine and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai, China. dryyz@sina.com.
authors.forename: Yong-yu
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Research Center for Traditional Chinese Medicine and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai, China. qhzhang@wayenbio.com.|School of Life Science and Technology, Tongji University, Shanghai, China. qhzhang@wayenbio.com.|Shanghai-MOST Key Laboratory of Health and Disease Genomics, National Engineering Center for Biochip at Shanghai, Shanghai, China. qhzhang@wayenbio.com.|State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. qhzhang@wayenbio.com.
authors.forename: Qing-hua
authors.initials: QH
authors.lastname: Zhang
mesh_terms: D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics* / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D005419:Flavonoids / Q000494:pharmacology*; D020441:Ginkgo biloba / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D034622:RNA Interference; D016329:Sp1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D005419:Flavonoids; D010936:Plant Extracts; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; C577474:CPT1A protein, human; D002334:Carnitine O-Palmitoyltransferase