Hepatic stellate cells role in the course of metabolic disorders development – A molecular overview

Bourebaba, Nabila; Marycz, Krzysztof

doi:10.1016/j.phrs.2021.105739

Cited by 31 publications

(20 citation statements)

References 37 publications

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“…Secretion of FABP4 from macrophages and injured endothelial cells has also been confirmed 13,14 , although the main source of circulating FABP4 level is adipocytes 8,12 . Kupffer cells and hepatic stellate cells in the liver have been reported to play significant roles in the development of NAFLD 31,32 . FABP4 was also reported to be expressed in Kupffer cells 33 and hepatic stellate cells 34 , as well as hepatocytes in hepatic cell carcinoma 35 , although secretion of FABP4 from those hepatic cells has not yet been proved.…”

Section: Discussionmentioning

confidence: 99%

Circulating level of fatty acid‐binding protein 4 is an independent predictor of metabolic dysfunction‐associated fatty liver disease in middle‐aged and elderly individuals

Tanaka

Takahashi

Higashiura

et al. 2022

J of Diabetes Invest

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Aims/Introduction Metabolic dysfunction‐associated fatty liver disease (MAFLD), defined as hepatosteatosis with type 2 diabetes mellitus, overweight/obesity or metabolic dysregulation, has been proposed as a new feature of chronic liver disease. Fatty acid‐binding protein 4 (FABP4) is expressed in adipose tissue, and secreted FABP4 is associated with the development of insulin resistance and atherosclerosis. However, the relationship between MAFLD and FABP4 has not been fully addressed. Materials and Methods Associations of MAFLD with metabolic markers, including FABP4, fibroblast growth factor 21 and adiponectin, were investigated in 627 individuals (men/women 292/335) in the Tanno‐Sobetsu Study, a population‐based cohort. Results The mean age was 65 years (range 19–98 years, median [interquartile range] 68 [56–76] years). Hepatosteatosis was determined by the fatty liver index (FLI), and FLI ≥35 for men and FLI ≥16 for women were used for detection of fatty liver, as previously reported using 14,471 Japanese individuals. FLI was positively correlated with systolic blood pressure and levels of FABP4 (r = 0.331, P < 0.001), fibroblast growth factor 21, homeostasis model assessment of insulin resistance as an insulin resistance index and uric acid, and was negatively correlated with levels of high‐density lipoprotein cholesterol and adiponectin. FABP4 concentration was independently associated with FLI after adjustment of age, sex, systolic blood pressure and levels of uric acid, high‐density lipoprotein cholesterol, homeostasis model assessment of insulin resistance, adiponectin and fibroblast growth factor 21 in multivariable regression analysis. Logistic regression analysis showed that FABP4 was an independent predictor of MAFLD after adjustment of age, sex, presence of diabetes mellitus, hypertension and dyslipidemia, and levels of uric acid, homeostasis model assessment of insulin resistance, adiponectin and fibroblast growth factor 21. Conclusions FABP4 concentration is independently associated with FLI and is an independent predictor of MAFLD in middle‐aged and elderly individuals.

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Section: Discussionmentioning

confidence: 99%

Circulating level of fatty acid‐binding protein 4 is an independent predictor of metabolic dysfunction‐associated fatty liver disease in middle‐aged and elderly individuals

Tanaka

Takahashi

Higashiura

et al. 2022

J of Diabetes Invest

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“…Liver is the core organ that regulates glucose and lipid metabolism. Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases and encompasses a wide range of downstream pathologies, including simple steatosis, steatohepatitis, advanced fibrosis, and cirrhosis [ 43 , 44 , 45 ]. After consumption of a high carbohydrate diet, patients with insulin resistance present lower glucose uptake and glycogen synthesis in skeletal muscle, leading to a doubling of both liver triglyceride levels and hepatic de novo lipogenesis [ 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

“…After being fed with the HF diet, the PTP1B −/− mice were resistant to weight gain and remained insulin sensitive, while the PTP1B +/+ mice rapidly gained weight and became insulin resistant [ 64 ]. PTP1B also participates in the development of the liver fibrosis and other metabolic disorders [ 44 ]. Deletion of the PTP1B gene could decrease fibrosis and inhibit collagen deposition by suppressing the expression of α-smooth muscle actin and collagen 1, suggesting that inhibition of PTP1B may prevent progression of hepatic steatosis to liver fibrosis [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…PTP1B also participates in the development of the liver fibrosis and other metabolic disorders [ 44 ]. Deletion of the PTP1B gene could decrease fibrosis and inhibit collagen deposition by suppressing the expression of α-smooth muscle actin and collagen 1, suggesting that inhibition of PTP1B may prevent progression of hepatic steatosis to liver fibrosis [ 44 ]. Taken together, PTP1B is considered as a negative regulator of insulin receptor signaling and PTP1B inhibitors become drug targets for metabolic diseases, such as diabetes and NAFLD.…”

Section: Discussionmentioning

confidence: 99%

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N-Octyl Caffeamide, a Caffeic Acid Amide Derivative, Prevents Progression of Diabetes and Hepatic Steatosis in High-Fat Diet Induced Obese Mice

Liu

Lee

et al. 2022

IJMS

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The underlying pathological mechanisms of diabetes are complicated and varied in diabetic patients, which may lead to the current medications often failing to maintain glycemic control in the long term. Thus, the discovery of diverse new compounds for developing medicines to treat diabetes and its complications are urgently needed. Polyphenols are metabolites of plants and have been employed in the prevention and treatment of a variety of diseases. Caffeic acid phenethyl ester (CAPE) is a category of compounds structurally similar to polyphenols. In this study, we aimed to investigate the antidiabetic activity and potential molecular mechanisms of a novel synthetic CAPE derivative N-octyl caffeamide (36M) using high-fat (HF) diet induced obese mouse models. Our results demonstrate that 36M prevented the progression of diabetes in the HF diet fed obese mice via increasing phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and inhibiting expression of protein tyrosine phosphatase 1B (PTP1B). We also found that 36M could prevent hepatic lipid storage in the HF diet fed mice via inhibition of fatty acid synthase and lipid droplet proteins, including perilipins and Fsp27. In conclusion, 36M is a potential candidate compound that can be developed as AMPK inhibitor and PTP1B inhibitor for treating diabetes and hepatic steatosis.

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“…Upon chronic liver injury, quiescent HSCs are activated and differentiated into myofibroblasts and secrete ECM. However, the activation and proliferation of HSCs are mainly responsible for the pathologic process of liver fibrogenesis or fibrosis [15]. ECM is a complex network structure composed of many macromolecules around cells, such as collagen, FN, laminin, elastin and proteoglycan.…”

Section: Discussionmentioning

confidence: 99%

miRNA-96-5p alleviates liver fibrosis by targeting FN1 and inhibiting ECM-receptor interaction pathway

Zhang

Gu²,

Jiang

et al. 2022

Preprint

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Background The abnormal expression of microRNAs (miRNAs) was involved in the pathological process of liver fibrosis, but their accurate molecular mechanisms remain to be fully clarified.Aim To evaluate the role of miRNA-96-5p (miR-96-5p) in hepatic stellate cells (HSCs) activation and liver fibrosis.Methods The differentially expressed mRNAs (DEMs) and signal pathways about hepatic fibrosis were analyzed and screened from Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to evaluate the biological significance and enriched pathways of the DEMs. The upstream miRNAs of DEMs were predicted by bioinformatics websites. The regulatory effects of miRNA on liver fibrosis through the target gene were verified in HSCs and in mouse CCl\(_4\)-induced liver fibrosis models.Results ECM-receptor interaction pathway was the most enriched pathway related to liver fibrosis through the GO and KEGG analysis of GEO database. Fibronectin1 (FN1) was up-regulated most significantly in the ECM-receptor pathway. Besides, miR-96-5p was considered to be the direct regulated miRNA of FN1 by bioinformatics websites prediction, qRT-PCR, Western blotting, and dual luciferase reporter assay. Finally, the effects of miR-96-5p up-regulation inhibit the activation of HSCs and alleviate CCl4-induced liver fibrosis by regulating FN1 and the ECM-receptor interaction pathway were confirmed in mice.Conclusions Our findings indicate that the up-regulation of miR-96-5p can inhibit activity of HSCs and alleviate liver fibrosis by inhibiting FN1 and ECM-receptor interaction pathway.

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Hepatic stellate cells role in the course of metabolic disorders development – A molecular overview

Cited by 31 publications

References 37 publications

Circulating level of fatty acid‐binding protein 4 is an independent predictor of metabolic dysfunction‐associated fatty liver disease in middle‐aged and elderly individuals

Circulating level of fatty acid‐binding protein 4 is an independent predictor of metabolic dysfunction‐associated fatty liver disease in middle‐aged and elderly individuals

N-Octyl Caffeamide, a Caffeic Acid Amide Derivative, Prevents Progression of Diabetes and Hepatic Steatosis in High-Fat Diet Induced Obese Mice

miRNA-96-5p alleviates liver fibrosis by targeting FN1 and inhibiting ECM-receptor interaction pathway

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