Olmesartan attenuates type 2 diabetes-associated liver injury: Cross-talk of AGE/RAGE/JNK, STAT3/SCOS3 and RAS signaling pathways

Nasr, Nesma M E Abo El; Saleh, Dalia O.; Mahmoud, Sawsan S.; Nofal, Salwa M.; Abdelsalam, Rania M.; Safar, Marwa M.; El‐Abhar, Hanan S.

doi:10.1016/j.ejphar.2020.173010

Cited by 33 publications

(29 citation statements)

References 49 publications

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“…IL6 (interleukin 6) was known as a marker gene for inflammation ( Fonseca et al, 2009 ). In the recent years, it was also found to regulate fat metabolism and related diseases through several pathways such as “Insulin resistance” ( Xuguang et al, 2019 ), “Non-alcoholic fatty liver disease” ( Fang et al, 2019 ), “AGE-RAGE signaling pathway in diabetic complications” ( Abo et al, 2020 ), “Lipid and atherosclerosis” ( Ridker et al, 2018 ) and “PI3K-Akt signaling pathway” ( Fajgenbaum et al, 2019 ). For instance, in “Non-alcoholic fatty liver disease” pathway, IL6 activates its receptor IL6R and regulates the activity of lipogenic enzymes through SOCS3 and SREBP-1c to influence de novo fatty acid synthesis.…”

Section: Discussionmentioning

confidence: 99%

Identifying Key Genes and Functionally Enriched Pathways of Diverse Adipose Tissue Types in Cattle

et al. 2022

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Background: Fat is a tissue that not just stores energy and plays a protective role; it is also a vital endocrine organ that generates and integrates signals to influence metabolism. Meanwhile, the excessive accumulation of lipids in adipose tissue can lead to metabolic disturbance and diseases. To date, the complicated molecular mechanisms of bovine adipose tissue are still unknown. This study aimed to identify key genes and functionally enriched pathways in various adipose tissue types.Results: The RNAseq data of 264 samples were downloaded from Gene Expression Omnibus (GEO) and analyzed by weighted gene co-expression network analysis (WGCNA). We identified 19 modules that significantly associated with at least one adipose tissue type. The brown module from GSE39618 was most closely associated with intramuscular fat tissue, which contained 550 genes. These genes were significantly enriched in pathways that related to inflammation and disease, such as TNF signaling pathway, IL-17 signaling pathway, and NF-kappa B signaling pathway. The pink module (GSE39618) that contained 58 genes was most closely associated with omental fat tissue. The turquoise (GSE39618), blue (GSE116775), and yellow (GSE65125) module were most closely associated with subcutaneous fat tissue. Genes in these modules were significantly enriched in pathways related to fat metabolism, such as the PPAR signaling pathway, fatty acid metabolism and PI3K-Akt signaling pathway. At last, key genes for intramuscular fat (PTGS2 and IL6), omental fat (ARHGEF5 and WT1), and subcutaneous fat (KIT, QR6Q1, PKD2L1, etc.) were obtained and verified. In addition, it was found that IL10 and VCAM1 might be potential genes to distinguish adipose and muscle.Conclusion: The study applied WGCNA to generate a landscape of adipose tissue and provide a basis for identifying potential pathways and hub genes of different adipose tissue types.

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Section: Discussionmentioning

confidence: 99%

Identifying Key Genes and Functionally Enriched Pathways of Diverse Adipose Tissue Types in Cattle

et al. 2022

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“…Oxidative stress and inflammation play an important role in the pathogenesis of HFr-induced metabolic changes and hepatic lesions [40]. In addition, increases in non-enzymatic protein glycation led formation of AGEs also play a role in HFr-induced toxicity [41]. AGEs affect structures and functions of proteins and cause further increases in oxidative stress and inflammation by interacting with their receptors [42].…”

Section: Discussionmentioning

confidence: 99%

The effect of 1,25-dihydroxyvitamin D3 on liver damage, oxidative stress, and advanced glycation end products in experimental nonalcoholic- and alcoholic- fatty liver disease

et al. 2021

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The effect of 1,25-dihydroxyvitamin D3 on liver damage, oxidative stress and advanced glycation end products in experimental nonalcoholic-and alcoholic-fatty liver disease Background/aim: Oxidative stress and advanced glycation end products (AGEs) formation are proposed as effective mechanisms in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). 1,25(OH)2D3 was proposed to have antioxidant, antiinflammatory and antiglycation properties. In this study, the effect of 1,25(OH)2 D3 treatment on oxidative stress parameters and AGEs levels together with hepatic histopathology was investigated in high fructose (HFr) or ethanol (EtOH)-treated rats. Materials and methods: Rats were treated with fructose (30%) or ethanol (5-20%) in drinking water with and without 1,25(OH)2D3 treatment (5 µg/kg two times a week) for 8 weeks. Insulin resistance (IR), oxidative stress parameters, AGEs, triglyceride (TG) and hydroxyproline (Hyp) levels together with histopathology were investigated in the liver. Results: 1,25(OH)2D3 decreased hepatic reactive oxygen species, lipid and protein oxidation products together with histopathological improvements in HFr-and EtOHtreated rats. 1,25(OH) 2 D 3 treatment was observed to decrease significantly serum and hepatic AGEs in HFr group, and hepatic AGEs in EtOH group. Conclusion: Our results clearly show that 1,25(OH)2 D3 treatment may be useful in the alleviation of hepatic lesions by decreasing glycooxidant stress in both NAFLD and ALD models created by HFr-and EtOH-treated rats, respectively.

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“…The CDI [ 87 ] analyzes the interaction between the combined and single groups using the following formula: CDI = AB/(A × B). In the pilot experiment, AB is the ratio of the combination insult group (HFFD + LPS) to normal control group (NFD) and A or B is the ratio of the HFFD or NFD/LPS group to the normal control group (NFD).…”

Section: Methodsmentioning

confidence: 99%

Palonosetron/Methyllycaconitine Deactivate Hippocampal Microglia 1, Inflammasome Assembly and Pyroptosis to Enhance Cognition in a Novel Model of Neuroinflammation

et al. 2021

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Since westernized diet-induced insulin resistance is a risk factor in Alzheimer’s disease (AD) development, and lipopolysaccharide (LPS) coexists with amyloid β (Aβ)1-42 in these patients, our AD novel model was developed to resemble sporadic AD by injecting LPS into high fat/fructose diet (HFFD)-fed rats. The neuroprotective potential of palonosetron and/or methyllycaconitine, 5-HT3 receptor and α7 nAChR blockers, respectively, was evaluated after 8 days of daily administration in HFFD/LPS rats. All regimens improved histopathological findings and enhanced spatial memory (Morris Water Maze); however, palonosetron alone or with methyllycaconitine promoted animal performance during novel object recognition tests. In the hippocampus, all regimens reduced the expression of glial fibrillary acidic protein and skewed microglia M1 to M2 phenotype, indicated by the decreased M1 markers and the enhanced M2 related parameters. Additionally, palonosetron and its combination regimen downregulated the expression of ASC/TMS1, as well as levels of inflammasome downstream molecules and abated cleaved caspase-1, interleukin (IL)-1β, IL-18 and caspase-11. Furthermore, ACh and 5-HT were augmented after being hampered by the insult. Our study speculates that blocking 5-HT3 receptor using palonosetron overrides methyllycaconitine to combat AD-induced neuroinflammation and inflammasome cascade, as well as to restore microglial function in a HFFD/LPS novel model for sporadic AD.

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Olmesartan attenuates type 2 diabetes-associated liver injury: Cross-talk of AGE/RAGE/JNK, STAT3/SCOS3 and RAS signaling pathways

Cited by 33 publications

References 49 publications

Identifying Key Genes and Functionally Enriched Pathways of Diverse Adipose Tissue Types in Cattle

Identifying Key Genes and Functionally Enriched Pathways of Diverse Adipose Tissue Types in Cattle

The effect of 1,25-dihydroxyvitamin D3 on liver damage, oxidative stress, and advanced glycation end products in experimental nonalcoholic- and alcoholic- fatty liver disease

Palonosetron/Methyllycaconitine Deactivate Hippocampal Microglia 1, Inflammasome Assembly and Pyroptosis to Enhance Cognition in a Novel Model of Neuroinflammation

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