PMID- 36415143 OWN - NLM STAT- MEDLINE DCOM- 20230307 LR - 20230307 IS - 1099-1573 (Electronic) IS - 0951-418X (Linking) VI - 37 IP - 3 DP - 2023 Mar TI - Pectolinarigenin shows lipid-lowering effects by inhibiting fatty acid biosynthesis in vitro and in vivo. PG - 913-925 LID - 10.1002/ptr.7679 [doi] AB - Pectolinarigenin is the main flavonoid compound and presents in Linaria vulgaris and Cirsium chanroenicum. In this study, RNA sequencing (RNA-seq) was applied to dissect the effect of pectolinarigenin on the transcriptome changes in the high lipid Huh-7 cells induced by oleic acid. RNA-seq results revealed that 15 pathways enriched by downregulated genes are associated with cell metabolism including cholesterol metabolism, glycerophospholipid metabolism, steroid biosynthesis, steroid hormone biosynthesis, fatty acid biosynthesis, etc. Moreover, 13 key genes related to lipid metabolism were selected. Among them, PPARG coactivator 1 beta (PPARGC1B) and carnitine palmitoyltransferase 1A (CPT1A) were found to be upregulated, solute carrier family 27 member 1(SLC27A1), acetyl-CoA carboxylase alpha (ACACA), fatty-acid synthase (FASN), 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR), etc. were found to be downregulated. Glycolysis/gluconeogenesis, steroid hormone biosynthesis, and fatty acid biosynthesis were all significantly downregulated, according to gene set variation analysis and gene set enrichment analysis. Besides, protein levels of FASN, ACACA, and SLC27A1 were all decreased, whereas PPARgamma and CPT1A were increased. Docking models showed that PPARgamma may be a target for pectolinarigenin. Furthermore, pectolinarigenin reduced serum TG and hepatic TG, and improved insulin sensitivity in vivo. Our findings suggest that pectolinarigenin may target PPARgamma and prevent fatty acid biosynthesis. CI - (c) 2022 John Wiley & Sons Ltd. FAU - Lan, Zhou AU - Lan Z AUID- ORCID: 0000-0001-7210-4181 AD - Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, Jiangxi Key Laboratory of Organic Chemistry, Jiangxi Science and Technology Normal University, Nanchang, China. FAU - Zhang, Kun AU - Zhang K AD - Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, Jiangxi Key Laboratory of Organic Chemistry, Jiangxi Science and Technology Normal University, Nanchang, China. FAU - He, Jianhui AU - He J AD - Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, Jiangxi Key Laboratory of Organic Chemistry, Jiangxi Science and Technology Normal University, Nanchang, China. FAU - Kang, Qiong AU - Kang Q AD - Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, Jiangxi Key Laboratory of Organic Chemistry, Jiangxi Science and Technology Normal University, Nanchang, China. FAU - Meng, Wei AU - Meng W AD - Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, Jiangxi Key Laboratory of Organic Chemistry, Jiangxi Science and Technology Normal University, Nanchang, China. FAU - Wang, Songhua AU - Wang S AUID- ORCID: 0000-0003-3605-4484 AD - Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, Jiangxi Key Laboratory of Organic Chemistry, Jiangxi Science and Technology Normal University, Nanchang, China. LA - eng GR - 31860605/National Natural Science Foundation of China/ GR - 81860692/National Natural Science Foundation of China/ PT - Journal Article DEP - 20221122 PL - England TA - Phytother Res JT - Phytotherapy research : PTR JID - 8904486 RN - 0 (pectolinarigenin) RN - 0 (PPAR gamma) RN - EC 2.3.1.85 (Fatty Acid Synthases) RN - 0 (Fatty Acids) RN - 0 (Lipids) RN - 0 (Steroids) RN - 0 (Hormones) SB - IM MH - *PPAR gamma/metabolism MH - *Liver MH - Lipid Metabolism MH - Fatty Acid Synthases/metabolism MH - Fatty Acids/pharmacology MH - Lipids MH - Steroids MH - Hormones/metabolism/pharmacology OTO - NOTNLM OT - RNA-seq OT - flavonoid OT - high fat diet OT - lipid OT - pectolinarigenin EDAT- 2022/11/24 06:00 MHDA- 2023/03/08 06:00 CRDT- 2022/11/23 01:43 PHST- 2022/10/21 00:00 [revised] PHST- 2022/08/05 00:00 [received] PHST- 2022/11/06 00:00 [accepted] PHST- 2022/11/24 06:00 [pubmed] PHST- 2023/03/08 06:00 [medline] PHST- 2022/11/23 01:43 [entrez] AID - 10.1002/ptr.7679 [doi] PST - ppublish SO - Phytother Res. 2023 Mar;37(3):913-925. doi: 10.1002/ptr.7679. Epub 2022 Nov 22.