Celastrol Reverses Palmitic Acid-Induced Insulin Resistance in HepG2 Cells via Restoring the miR-223 and GLUT4 Pathway

Zhang, Xue; Xue, Xiaocheng; Wang, Ying; Cao, Fanfan; You, Jun; Uzan, Georges; Peng, Bin; Zhang, Denghai

doi:10.1016/j.jcjd.2018.07.002

Cited by 22 publications

(15 citation statements)

References 40 publications

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“…After ETO was used, the oxidative decomposition of fatty acid was weakened. In healthy rats, PA increased the myocardial contractility, which could be blocked by ETO [17,18]. In hypertensive rats, the effect of PA on the myocardial contractility disappeared, yet nNOS activity of protein expression was raised, and administration of nNOS inhibitor and CPT-1 inhibitor could inhibit the positive inotropic effect of PA on left ventricular cardiomyocytes in hypertensive rats, which meant that increased nNOS in hypertensive rats inhibited the positive inotropic effect of PA on cardiomyocytes, and it was related to protein of CPT-1.…”

Section: Discussionmentioning

confidence: 93%

Molecular Mechanism of Palmitic Acid on Myocardial Contractility in Hypertensive Rats and Its Relationship with Neural Nitric Oxide Synthase Protein in Cardiomyocytes

Tan

Song

et al. 2021

BioMed Research International

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Objective. It is aimed at investigating the mechanism of palmitic acid (PA) on myocardial contractility in hypertensive rats and its relationship with myocardial neural nitric oxide synthase (nNOS) protein. Methods. The rats were randomly divided into sham operation group and hypertensive group, with thirty rats in each group, to prepare angiotensin II-induced hypertensive model rats. The blood pressure of rats was measured by the multianimal multichannel tail cuff noninvasive blood pressure system of Kent Coda, USA. The Ionoptix single-cell contraction detection system was used to detect myocardial cells. ATP level of left ventricular cardiomyocytes was determined by luminescence method, and protein was measured by Western blot. Results. Compared with the sham group, systolic blood pressure and diastolic blood pressure were increased in the hypertensive group over 4 weeks; PA increased the contractility of left ventricular cardiomyocytes in normal rats, but not in hypertensive rats, and PA increased the intracellular ATP level of rats in the sham group but not in the hypertension group. In the hypertension group, the expression of nNOS in the cardiomyocytes was significantly increased, and specific nNOS inhibitor S-methyl-L-thiocitrulline (SMTC) was found to restore the positive inotropic effect of PA in the myocardium of the hypertension group. PA was supplemented after using CPT-1 inhibitor etomoxir (ETO); it was found that ETO inhibited the positive inotropic effect of PA on left ventricular cardiomyocytes in the sham group, and PA was supplemented after using SMTC and ETO, it was found that SMTC + ETO could inhibit the positive inotropic effect of PA on left ventricular cardiomyocytes in myocardium of hypertensive rats. Conclusion. PA could increase the contractility of healthy cardiomyocytes, but had no obvious positive effect on the cardiomyocytes of hypertensive rats, PA enhanced the contractility of cardiomyocytes by increasing ATP level in them, and the inhibitory effect of PA on myocardial contractility in hypertensive rats may be related to the increased nNOS and CPT-1 in cardiomyocytes.

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Section: Discussionmentioning

confidence: 93%

Molecular Mechanism of Palmitic Acid on Myocardial Contractility in Hypertensive Rats and Its Relationship with Neural Nitric Oxide Synthase Protein in Cardiomyocytes

Tan

Song

et al. 2021

BioMed Research International

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“…Compared with the insulin resistance group, miR-93-5p overexpression markedly increased glucose uptake, cell proliferation, and glycogen synthesis [ 42 ]. Celastrol reversed palmitic acid-induced insulin resistance by restoring the miR-223 and GLUT4 pathways [ 43 ]. Shu et al (2020) reported that resveratrol significantly increased p-PI3K and p-AKT expression levels in miR-363 mimic-transfected HepG2 cells.…”

Section: Resultsmentioning

confidence: 99%

Taxifolin and Sorghum Ethanol Extract Protect against Hepatic Insulin Resistance via the miR-195/IRS1/PI3K/AKT and AMPK Signalling Pathways

Lee

Jeong

et al. 2021

Antioxidants

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This study aimed to evaluate the effects of taxifolin and sorghum ethanol extract on free fatty acid (FFA)-induced hepatic insulin resistance. FFA treatment decreased glucose uptake by 16.2% compared with that in the control, whereas taxifolin and sorghum ethanol extract increased the glucose uptake. Additionally, taxifolin and sorghum ethanol extract increased the expression of p-PI3K, p-IRS1, p-AKT, p-AMPK, and p-ACC in FFA-induced hepatocytes. Furthermore, FFA treatment increased the expression of miR-195. However, compared with the FFA treatment, treatment with taxifolin and sorghum ethanol extract decreased miR-195 expression in a dose-dependent manner. Taxifolin and sorghum ethanol extract enhanced p-IRS1, p-PI3K, p-AMPK, p-AKT, and p-ACC expression by suppressing miR-195 levels in miR-195 mimic- or inhibitor-transfected cells. These results indicate that taxifolin and sorghum ethanol extract attenuate insulin resistance by regulating miR-195 expression, which suggests that taxifolin and sorghum ethanol extract may be useful antidiabetic agents.

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“…Furthermore, celastrol regulates the expression of some miRNAs involved in the regulation of insulin ( 42 , 43 ). For example, celastrol reverses the role of Palmitic acid in inhibiting expression levels of GLUT4 ( 44 ). More recently, it was demonstrated that MET treatment increases expression levels of GLUT4 in the endometrium of patients with PCOS and EH ( 7 ).…”

Section: Discussionmentioning

confidence: 99%

Role of metformin in functional endometrial hyperplasia and polycystic ovary syndrome involves the regulation of MEG3/miR‑223/GLUT4 and SNHG20/miR‑4486/GLUT4 signaling

et al. 2022

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Metformin (MET) can effectively treat endometrial hyperplasia (EH), and the expression of glucose transporter type 4 insulin-responsive (GLUT4) is closely associated with the development of EH. The present study aimed to verify the effect of MET in functional EH and polycystic ovary syndrome (PCOS). H&E staining was performed to analyze the severity of EH, and immunohistochemistry was performed to evaluate the expression of GLUT4 in the endometrium of PCOS rats. Reverse transcription-quantitative PCR was used to calculate the expression of long non-coding (lnc)RNA-maternally expressed gene 3 (MEG3), lncRNA-small nucleolar RNA host gene 20 (SNHG20), GLUT4 mRNA, microRNA (miR)-223 and miR-4486. Sequence analysis and luciferase assays were performed to explore the regulatory relationship among certain lncRNAs, miRNAs and target genes. EH in PCOS rats was efficiently inhibited by MET administration. The increased expression of GLUT4 in PCOS rats was attenuated by MET treatment. Moreover, the expression levels of lncRNA-MEG3 and lncRNA-SNHG20 were significantly inhibited in the endometrium of PCOS rats. MET treatment also showed remarkable efficiency in restoring the expression of lncRNA-MEG3 and lncRNA-SNHG20. Meanwhile, the expression levels of miR-223 and miR-4486 were notably elevated in the endometrium of PCOS rats, while MET treatment reduced the expression of miR-223 and miR-4486 in PCOS rats. Furthermore, a luciferase assay confirmed the inhibitory relationship between miR-223 and lncRNA-MEG3/GLUT4 expression, as well as between miR-4486 and lncRNA-SNHG20/GLUT4 expression. GLUT4 knockdown restored the decreased viability of HCC-94 cells induced by overexpression of lncRNA-MEG3. To conclude, MET exhibited a therapeutic effect in the treatment of EH by modulating the lncRNA-MEG3/miR-223/GLUT4 and lncRNA-SNHG20/miR-4486/GLUT4 signaling pathways. This work provides mechanistic insight into the development of EH.

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Celastrol Reverses Palmitic Acid-Induced Insulin Resistance in HepG2 Cells via Restoring the miR-223 and GLUT4 Pathway

Cited by 22 publications

References 40 publications

Molecular Mechanism of Palmitic Acid on Myocardial Contractility in Hypertensive Rats and Its Relationship with Neural Nitric Oxide Synthase Protein in Cardiomyocytes

Molecular Mechanism of Palmitic Acid on Myocardial Contractility in Hypertensive Rats and Its Relationship with Neural Nitric Oxide Synthase Protein in Cardiomyocytes

Taxifolin and Sorghum Ethanol Extract Protect against Hepatic Insulin Resistance via the miR-195/IRS1/PI3K/AKT and AMPK Signalling Pathways

Role of metformin in functional endometrial hyperplasia and polycystic ovary syndrome involves the regulation of MEG3/miR‑223/GLUT4 and SNHG20/miR‑4486/GLUT4 signaling

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