PMID- 25183267 OWN - NLM STAT- MEDLINE DCOM- 20150716 LR - 20231213 IS - 1423-0127 (Electronic) IS - 1021-7770 (Print) IS - 1021-7770 (Linking) VI - 21 IP - 1 DP - 2014 Sep 3 TI - Flavonoid ingredients of Ginkgo biloba leaf extract regulate lipid metabolism through Sp1-mediated carnitine palmitoyltranferase 1A up-regulation. PG - 87 LID - 10.1186/s12929-014-0087-x [doi] LID - 87 AB - 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 beta-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. CONCLUSION: 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. FAU - Wei, Ting AU - Wei T AD - Research Center for Traditional Chinese Medicine and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai, China. ting_life@126.com. AD - Shanghai-MOST Key Laboratory of Health and Disease Genomics, National Engineering Center for Biochip at Shanghai, Shanghai, China. ting_life@126.com. FAU - Xiong, Fei-fei AU - Xiong FF AD - School of Life Science and Technology, Tongji University, Shanghai, China. f_ashley@163.com. AD - Shanghai-MOST Key Laboratory of Health and Disease Genomics, National Engineering Center for Biochip at Shanghai, Shanghai, China. f_ashley@163.com. FAU - Wang, Shi-dong AU - Wang SD AD - Research Center for Traditional Chinese Medicine and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai, China. sdwang@wayenbio.com. AD - Shanghai-MOST Key Laboratory of Health and Disease Genomics, National Engineering Center for Biochip at Shanghai, Shanghai, China. sdwang@wayenbio.com. FAU - Wang, Ke AU - Wang K AD - Shanghai-MOST Key Laboratory of Health and Disease Genomics, National Engineering Center for Biochip at Shanghai, Shanghai, China. wangke8430@163.com. FAU - Zhang, Yong-yu AU - Zhang YY AD - Research Center for Traditional Chinese Medicine and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai, China. dryyz@sina.com. FAU - Zhang, Qing-hua AU - Zhang QH AD - Research Center for Traditional Chinese Medicine and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai, China. qhzhang@wayenbio.com. AD - School of Life Science and Technology, Tongji University, Shanghai, China. qhzhang@wayenbio.com. AD - Shanghai-MOST Key Laboratory of Health and Disease Genomics, National Engineering Center for Biochip at Shanghai, Shanghai, China. qhzhang@wayenbio.com. AD - State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. qhzhang@wayenbio.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140903 PL - England TA - J Biomed Sci JT - Journal of biomedical science JID - 9421567 RN - 0 (Flavonoids) RN - 0 (Plant Extracts) RN - 0 (Sp1 Transcription Factor) RN - 0 (SP1 protein, human) RN - EC 2.3.1.21 (CPT1A protein, human) RN - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase) SB - IM MH - Carnitine O-Palmitoyltransferase/*genetics/metabolism MH - Chromatin Immunoprecipitation MH - Electrophoretic Mobility Shift Assay MH - Flavonoids/*pharmacology MH - Ginkgo biloba/*chemistry MH - Hep G2 Cells MH - Humans MH - Lipid Metabolism/*drug effects MH - Plant Extracts/pharmacology MH - Plant Leaves/chemistry MH - RNA Interference MH - Sp1 Transcription Factor/*genetics/metabolism MH - Up-Regulation/*drug effects PMC - PMC4428510 EDAT- 2014/09/04 06:00 MHDA- 2015/07/17 06:00 PMCR- 2014/09/03 CRDT- 2014/09/04 06:00 PHST- 2014/04/24 00:00 [received] PHST- 2014/08/21 00:00 [accepted] PHST- 2014/09/04 06:00 [entrez] PHST- 2014/09/04 06:00 [pubmed] PHST- 2015/07/17 06:00 [medline] PHST- 2014/09/03 00:00 [pmc-release] AID - s12929-014-0087-x [pii] AID - 87 [pii] AID - 10.1186/s12929-014-0087-x [doi] PST - epublish SO - J Biomed Sci. 2014 Sep 3;21(1):87. doi: 10.1186/s12929-014-0087-x.