PMID- 34563954 OWN - NLM STAT- MEDLINE DCOM- 20220124 LR - 20220124 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 143 DP - 2021 Nov TI - Transcriptome analysis to reveal the mechanism of the effect of Echinops latifolius polysaccharide B on palmitate-induced insulin-resistant. PG - 112203 LID - S0753-3322(21)00987-2 [pii] LID - 10.1016/j.biopha.2021.112203 [doi] AB - Hepatic insulin resistance is a crucial pathological process in type 2 diabetes mellitus (T2DM) associated with visceral adiposity and metabolic disorders. Echinops latifolius polysaccharide B (ETPB), a polysaccharide extracted from Echinops latifolius Tausch, increases insulin sensitivity in the high-fat diet-fed and STZ induced SD rat model and even prevented hepatic metabolic disorders. However, the mechanism by which ETPB improves carbohydrate and lipid metabolisms in the liver with insulin resistance remains largely unknown. In the present work, an lnsulin resistance cell model (IR-HepG2) was established. Glucose consumption, glycogen content, triglycerides (TG), and free fatty acids (FFAs) levels were detected. The result revealed that the intervention of ETPB significantly increased glucose consumption and glycogen synthesis and reduced FFAs and TG production in IR-HepG2 cells. Further, we also employed RNA-seq to identify differentially expressed miRNAs (DEMs) and mRNAs (DEGs) with a fold change of >/= 1.5 and p-value of <0.05. Finally, we identified 1028, 682, 382, 1614, 519 and 825 DEGs, and 71, 113, 94, 68, 52 and 38 DEMs in different comparisons, respectively. Based on a short time-series expression miner (STEM) analysis, six profiles were chosen for further analysis. Seventeen insulin resistance-associated dynamic DEGs were identified during ETPB stimulation. Based on these dynamic DEGs, the related miRNAs were acquired from DEMs, and an integrated miRNA-mRNA regulatory network was subsequently constructed. Besides, some DEGs and DEMs were validated using qPCR. This study provides transcriptomic evidence of the molecular mechanism involved in HepG2 insulin resistance, leading to the discovery of miRNA-based target therapies for ETPB. CI - Copyright (c) 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved. FAU - Li, Ran AU - Li R AD - College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, PR China. FAU - Xia, Yajuan AU - Xia Y AD - Inner Mongolia Comprehensive Center for Disease Control and Prevention, Hohhot, Inner Mongolia, PR China. FAU - Gao, Zhenzhen AU - Gao Z AD - College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, PR China. FAU - Song, Yue AU - Song Y AD - College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, PR China. FAU - Guo, Zhiwei AU - Guo Z AD - Inner Mongolia Comprehensive Center for Disease Control and Prevention, Hohhot, Inner Mongolia, PR China. FAU - Yang, Ying AU - Yang Y AD - College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, PR China. Electronic address: yangyingzsy@126.com. LA - eng PT - Journal Article DEP - 20210924 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Hypoglycemic Agents) RN - 0 (MicroRNAs) RN - 0 (Palmitates) RN - 0 (Plant Extracts) RN - 0 (Polysaccharides) SB - IM MH - *Echinops Plant/chemistry MH - Energy Metabolism/drug effects MH - *Gene Expression Profiling MH - Hep G2 Cells MH - Hepatocytes/*drug effects/metabolism MH - Humans MH - Hypoglycemic Agents/isolation & purification/*pharmacology MH - *Insulin Resistance/genetics MH - MicroRNAs/genetics/metabolism MH - Palmitates/*toxicity MH - Plant Extracts/isolation & purification/*pharmacology MH - Polysaccharides/isolation & purification/*pharmacology MH - RNA-Seq MH - *Transcriptome OTO - NOTNLM OT - ETPB OT - HepG2 OT - Insulin resistance OT - MiRNAs OT - RNA sequencing EDAT- 2021/09/27 06:00 MHDA- 2022/01/27 06:00 CRDT- 2021/09/26 20:54 PHST- 2021/07/29 00:00 [received] PHST- 2021/09/08 00:00 [revised] PHST- 2021/09/13 00:00 [accepted] PHST- 2021/09/27 06:00 [pubmed] PHST- 2022/01/27 06:00 [medline] PHST- 2021/09/26 20:54 [entrez] AID - S0753-3322(21)00987-2 [pii] AID - 10.1016/j.biopha.2021.112203 [doi] PST - ppublish SO - Biomed Pharmacother. 2021 Nov;143:112203. doi: 10.1016/j.biopha.2021.112203. Epub 2021 Sep 24.