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CTRP13 attenuates the expression of LN and CAV-1 Induced by high glucose via CaMKK?/AMPK pathway in rLSECs.

ABSTRACT: OBJECTIVE:To investigate the effect and mechanism of CTRP13 on hepatic sinusoidal capillarization induced by high glucose in rat liver sinusoidal endothelial cells (rLSECs). RESULTS:CTRP13 was reduced in high glucose-treated rLSECs. High glucose increased LN and CAV-1 expression and inhibited CaMKK? and AMPK phosphorylation. CTRP13 overexpression protected rLSECs against high glucose-induced increase of LN and CAV-1 expression. Moreover, CTRP13 overexpression increased high glucose-induced inhibition of CaMKK? and AMPK activation in CTRP13-overexpressing rLSECs. Inhibition of CaMKK? and AMPK disturbed the protective effects of CTRP13 in high glucose-induced increase of LN and CAV-1. Hepatic steatosis was enhanced and basement membrane was thickened in liver of diabetic fatty liver rats. CONCLUSIONS:Our data identified the protective role of CTRP13 in hepatic sinusoidal capillarization induced by high glucose via activating CAMKK?/AMPK pathway. CTRP13 may be a potential target for screening and treating diabetic fatty liver. METHODS:Construct lentiviral CTRP13 overexpression vector and transfect rLSECs. Use STO-609 (a CaMKK? inhibitor) or Compound C (an AMPK inhibitor) to treat rLSECs. CTRP13, CaMKK?, AMPK, laminin (LN) and caveolin-1 (CAV-1) were detected by qRT-PCR and Western blotting. Establish rat model of diabetic fatty liver. Use immunohistochemistry, hematoxylin-eosin and silver staining to observe the histopathological features of liver.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC7343496 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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CTRP13 attenuates the expression of LN and CAV-1 Induced by high glucose via CaMKKβ/AMPK pathway in rLSECs.

Zhang Qi Q Niu Xiang'e X Tian Limin L Liu Jing J Niu Ruilan R Quan Jinxing J Yu Jing J Lin Wenyan W Qian Zibing Z Zeng Peiyun P

Aging 20200617 12

<h4>Objective</h4>To investigate the effect and mechanism of CTRP13 on hepatic sinusoidal capillarization induced by high glucose in rat liver sinusoidal endothelial cells (rLSECs).<h4>Results</h4>CTRP13 was reduced in high glucose-treated rLSECs. High glucose increased LN and CAV-1 expression and inhibited CaMKKβ and AMPK phosphorylation. CTRP13 overexpression protected rLSECs against high glucose-induced increase of LN and CAV-1 expression. Moreover, CTRP13 overexpression increased high glucos ...[more]

PMID: 32554851

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Project description:Subject: Cardiovascular disease, as a very common and serious coexisting disease in diabetic patients, and is one of the risk factors that seriously affect the prognosis and complications of surgical patients. Previous studies have shown that sevoflurane post-conditioning (SPostC) exerts a protective effect against myocardial ischemia/reperfusion injury by HIF-1α, but the protective effect is weakened or even disappeared under hyperglycemia. This study aims to explore whether regulating the HIF-1α/MIF/AMPK signaling pathway can restore the protective effect and reveal the mechanism of SPostC on cardiomyocyte hypoxia/reoxygenation injury under high glucose conditions. Methods: H9c2 cardiomyocytes were cultured in normal and high-concentration glucose medium to establish a hypoxia/reoxygenation (H/R) injury model of cardiomyocytes. SPostC was performed with 2.4% sevoflurane for 15 min before reoxygenation. Cell damage was determined by measuring cell viability, lactate dehydrogenase activity, and apoptosis; Testing cell energy metabolism by detecting reactive oxygen species (ROS) generation, ATP content and mitochondrial membrane potential; Analysis of the change of HIF-1α, MIF and AMPKα mRNA expression by RT-PCR. Western blotting was used to examine the expression of HIF-1α, MIF, AMPKα and p-AMPKα proteins. HIF-1α and MIF inhibitors and agonists were administered 40 min before hypoxia. Results: 1) SPostC exerts a protective effect by increasing cell viability, reducing LDH levels and cell apoptosis under low glucose (5 μM) after undergoing H/R injury; 2) High glucose concentration (35 μM) eliminated the cardioprotective effect of SPostC, which is manifested by a significantly decrease in the protein and mRNA expression level of the HIF-1α/MIF/AMPK signaling pathway, accompanied by decreased cell viability, increased LDH levels and apoptosis, increased ROS production, decreased ATP synthesis, and decreased mitochondrial membrane potential; 3. Under high glucose (35 μM), the expression levels of HIF-1α and MIF were up-regulated by using agonists, which can significantly increase the level of p-AMPKα protein, and the cardioprotective effect of SPostC was restored. Conclusion: The signal pathway of HIF-1α/MIF/AMPK of H9c2 cardiomyocytes may be the key point of SPostC against H/R injure. The cardioprotective of SPostC could be restored by upregulating the protein expression of HIF-1α and MIF under hyperglycemia.

Project description:BackgroundL-theanine, a non-protein amino acid was found principally in the green tea, has been previously shown to exhibit potent anti-obesity property and hepatoprotective effect. Herein, we investigated the effects of L-theanine on alleviating nonalcoholic hepatic steatosis in vitro and in vivo, and explored the underlying molecular mechanism.MethodsIn vitro, HepG2 and AML12 cells were treated with 500 μM oleic acid (OA) or treated with OA accompanied by L-theanine. In vivo, C57BL/6J mice were fed with normal control diet (NCD), high-fat diet (HFD), or HFD along with L-theanine for 16 weeks. The levels of triglycerides (TG), accumulation of lipid droplets and the expression of genes related to hepatocyte lipid metabolic pathways were detected in vitro and in vivo.ResultsOur data indicated that, in vivo, L-theanine significantly reduced body weight, hepatic steatosis, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), TG and LDL cholesterol (LDL-C) in HFD-induced nonalcoholic fatty liver disease (NAFLD) mice. In vitro, L-theanine also significantly alleviated OA induced hepatocytes steatosis. Mechanic studies showed that L-theanine significantly inhibited the nucleus translocation of sterol regulatory element binding protein 1c (SREBP-1c) through AMPK-mTOR signaling pathway, thereby contributing to the reduction of fatty acid synthesis. We also identified that L-theanine enhanced fatty acid β-oxidation by increasing the expression of peroxisome proliferator-activated receptor α (PPARα) and carnitine palmitoyltransferase-1 A (CPT1A) through AMP-activated protein kinase (AMPK). Furthermore, our study indicated that L-theanine can active AMPK through its upstream kinase Calmodulin-dependent protein kinase kinase-β (CaMKKβ).ConclusionsTaken together, our findings suggested that L-theanine alleviates nonalcoholic hepatic steatosis by regulating hepatocyte lipid metabolic pathways via the CaMKKβ-AMPK signaling pathway.

Dataset Information

CTRP13 attenuates the expression of LN and CAV-1 Induced by high glucose via CaMKK?/AMPK pathway in rLSECs.

Publications

CTRP13 attenuates the expression of LN and CAV-1 Induced by high glucose via CaMKKβ/AMPK pathway in rLSECs.

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