CtBP2 ameliorates palmitate-induced insulin resistance in HepG2 cells through ROS mediated JNK pathway

Liu, Pingli; Shi, Li; Cang, Xiaomin; Huang, Jieru; Wu, Xianwei; Jin, Yan; Chen, Ling; Cui, Shiwei; Ye, Xinhua

doi:10.1016/j.ygcen.2017.01.018

Cited by 17 publications

(14 citation statements)

References 35 publications

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“…The up-regulated NOX2 enzyme contributes to oxidative stress and cardiovascular disease [20]. Consistent with previous studies in other cell types [21], we also found that PA promoted ROS generation in H9c2 cells, suggesting that oxidative stress may be one of the reasons for PA-induced H9c2 cell apoptosis.…”

Section: Discussionsupporting

confidence: 91%

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Oxidative and endoplasmic reticulum stresses are involved in palmitic acid-induced H9c2 cell apoptosis

et al. 2019

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Palmitic acid (PA) is the most common saturated long-chain fatty acid that causes damage to heart muscle cells. However, the molecular mechanism of PA toxicity in myocardial cells is not fully understood. In the present study, we explored the effects of PA on proliferation and apoptosis of H9c2 cardiomyocytes, and uncovered the signaling pathways involved in PA toxicity. Our study revealed induction of both oxidative and endoplasmic reticulum (ER) stresses and exacerbation of apoptosis in PA-treated H9c2 cells. Inhibition of oxidative stress by N-acetylcysteine (NAC) reduced apoptosis and decreased ER stress in PA-treated H9c2 cells. Moreover, inhibition of ER stress by 4-phenyl butyric acid decreased apoptosis and attenuated oxidative stress. In summary, the present study demonstrated that oxidative stress coordinates with ER stress to play important roles in PA-induced H9c2 cell apoptosis.

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Section: Discussionsupporting

confidence: 91%

“…Previous studies have also shown that oxidative and ER stresses are closely related [15,16]. Both oxidative stress [21] and ER stress [9] are involved in PA-induced apoptosis. However, there is little known about the relationship between oxidative and ER stresses in PA-induced H9c2 cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Oxidative and endoplasmic reticulum stresses are involved in palmitic acid-induced H9c2 cell apoptosis

et al. 2019

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“…AGRP has been reported to play similar roles in food intake and high-fat diet preference as NPY in mice and bats, and the upregulation of the agrp gene enhances diet preference and fat gain (Levin et al, 2013). The ctbp2 gene was downregulated and highly methylated in the high-PUFA content group, which agrees with the findings of previous studies that overexpression of C-terminal-binding protein 2 (CTBP2) suppresses lipid accumulation and hepatic glucose uptake (Liu et al, 2017). Fewer correlated genes were identified from the liver and muscle data, partly because of the limited number of samples.…”

Section: Discussionsupporting

confidence: 91%

Genomic, Transcriptomic, and Epigenomic Features Differentiate Genes That Are Relevant for Muscular Polyunsaturated Fatty Acids in the Common Carp

Zhang

Jiang

et al. 2019

Front. Genet.

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Polyunsaturated fatty acids (PUFAs) are a set of important nutrients that mainly include arachidonic acid (ARA4), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and α-linolenic acid (ALA). Recently, fish-derived PUFAs have been associated with cardiovascular health, fetal development, and improvement of brain functions. Studies have shown that fish muscular tissues are rich in PUFAs, which are influenced by various factors, including genetic variations, regulatory profiles, and methylation status of desaturase genes during fatty acid desaturation and elongation processes. However, the genetic mechanism and the pathways involved in fatty acid metabolism in fishes remain unclear. The overall aim of this study was to assess differences in gene expression responses among fishes with different fatty acid levels. To achieve this goal, we conducted genome-wide association analysis (GWAS) using a 250K SNP array in a population of 203 samples of common carp (Cyprinus carpio) and identified nine SNPs and 15 genes associated with muscular PUFA content. Then, RNA-Seq and whole genome bisulfite sequencing (WGBS) of different groups with high and low EPA, DHA, ARA4, and ALA contents in muscle, liver and brain tissues were conducted, resulting in 6,750 differentially expressed genes and 5,631 genes with differentially methylated promoters. Gene ontology and KEGG pathway enrichment analyses of RNA-Seq and WGBS results identified enriched pathways for fatty acid metabolism, which included the adipocytokine signaling pathway, ARA4 and linoleic acid metabolism pathway, and insulin signaling pathway. Integrated analysis indicated significant correlations between gene expression and methylation status among groups with high and low PUFA contents in muscular tissues. Taken together, these multi-level results uncovered candidate genes and pathways that are associated with fatty acid metabolism and paved the way for further genomic selection and carp breeding for PUFA traits.

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“…6) The core of T2DM pathophysiology, as demonstrated by several studies, incorporates the deposition of lipid metabolites in the hepatic system and skeletal muscles because of raised plasma free fatty acids (FFAs), which are closely related to IR. 4,[7][8][9][10][11] Moreover, circulating FFAs and their metabolites can directly enter the liver, and inhibit insulin-stimulated uptake of glucose and glycogen production via interfering with the insulin signaling system. 12,13) Palmitic acid (PA) is one of the most distributed FFAs in human plasma, accounting for around 30% of total FFAs, and it has been demonstrated to mediate IR in cultured HepG2 cells.…”

Section: Introductionmentioning

confidence: 99%

Quercetin-3-O-α-L-arabinopyranosyl-(1→2)-β-D-glucopyranoside Isolated from Eucommia ulmoides Leaf Relieves Insulin Resistance in HepG2 Cells via the IRS-1/PI3K/Akt/GSK-3β Pathway

Tang

Liu

et al. 2023

Biological & Pharmaceutical Bulletin

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For nearly 2000 years, Eucommia ulmoides Oliver (EUO) has been utilized in traditional Chinese medicine (TCM) throughout China. Flavonoids present in bark and leaves of EUO are responsible for their antioxidant, anti-inflammatory, antitumor, anti-osteoporosis, hypoglycemic, hypolipidemic, antibacterial, and antiviral properties, but the main bioactive compound has not been established yet. In this study, we isolated and identified quercetin glycoside (QAG) from EUO leaves (EUOL) and preliminarily explored its molecular mechanism in improving insulin resistance (IR). The results showed that QAG increased uptake of glucose as well as glycogen production in the palmitic acid (PA)-induced HepG2 cells in a dose-dependent way. Further, we observed that QAG increases glucose transporters 2 and 4 (GLUT2 and GLUT4) expression and suppresses the phosphorylation of insulin receptor substrate (IRS)-1 at serine 612 , thus promoting the expression of phosphatidylinositol-3-kinase (PI3K) at tyrosine 458 and tyrosine 199 , as well as protein kinase B (Akt) and glycogen synthase kinase (GSK)-3β at serine 473 and serine 9 , respectively. The influence posed by QAG on the improvement of uptake of glucose was significantly inhibited by LY294002, a PI3K inhibitor. In addition, the molecular docking result showed that QAG could bind to insulin receptors. In summary, our data established that QAG improved IR as demonstrated by the increased uptake of glucose and glycogen production through a signaling pathway called IRS-1/PI3K/Akt/GSK-3β.

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CtBP2 ameliorates palmitate-induced insulin resistance in HepG2 cells through ROS mediated JNK pathway

Cited by 17 publications

References 35 publications

Oxidative and endoplasmic reticulum stresses are involved in palmitic acid-induced H9c2 cell apoptosis

Oxidative and endoplasmic reticulum stresses are involved in palmitic acid-induced H9c2 cell apoptosis

Genomic, Transcriptomic, and Epigenomic Features Differentiate Genes That Are Relevant for Muscular Polyunsaturated Fatty Acids in the Common Carp

Quercetin-3-<i>O</i>-α-L-arabinopyranosyl-(1→2)-β-D-glucopyranoside Isolated from <i>Eucommia ulmoides</i> Leaf Relieves Insulin Resistance in HepG2 Cells <i>via</i> the IRS-1/PI3K/Akt/GSK-3β Pathway

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