Emerging roles of angiopoietin‐like proteins in inflammation: Mechanisms and potential as pharmacological targets

Yang, Jinqiang; Song, Qiu-Yi; Niu, Shu-Xuan; Chen, Huijing; Petersen, Robert B.; Huang, Kun

doi:10.1002/jcp.30534

Cited by 21 publications

(19 citation statements)

References 152 publications

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“…19,20 Recent studies have reported the role of ANGPTL8/betatrophin in nuclear factor-kappaB (NF-kappaB) mediated inflammation. [21][22][23] Thus the newly identified atypical member of ANGPTL family, ANGPTL8/betatrophin, may also be an inflammatory marker in insulin resistance and related diseases, which contributes to a better understanding of the role of ANGPTL8/ betatrophin in T2DM. But the mechanism of ANGPTL8/ betatrophin in regulating glucose metabolism remains unclear.…”

Section: Introductionmentioning

confidence: 99%

ANGPTL8/Betatrophin Improves Glucose Tolerance in Older Mice and Metabolomic Analysis Reveals Its Role in Insulin Resistance in HepG2 Cells

Xu¹,

Wang²,

Li³

et al. 2021

DMSO

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Background: Insulin resistance is a determining factor in the pathophysiology of type 2 diabetes mellitus (T2DM). Angiopoietin-like protein 8 (ANGPTL8, also known as betatrophin), associated with glucose homeostasis and lipid metabolism, has attracted attention. But its mechanism in glucose metabolism remains unclear. This study aimed to explore the effect of ANGPTL8/betatrophin on glucose tolerance in Kunming (KM) mice of different ages and metabolic profiles in insulin-resistant HepG2 cells. Our study may provide a new perspective of ANGPTL8/betatrophin in insulin resistance from the metabolic changes. Methods: Oral glucose tolerance test was performed in KM mice of different ages. Insulin concentration was measured by using a quantitative enzyme-linked immunosorbent assay (ELISA). ANGPTL8/betatrophin knockouts in HepG2 cells were established with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) protein 9 (CRISPR/Cas9) system. Cell counting kit-8 (CCK-8) assay was used to determine cell viability after gene knockout. The effect of ANGPTL8/betatrophin on the metabolomic changes was evaluated in high insulin-induced insulin-resistant HepG2 cells by an ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Results: ANGPTL8/betatrophin improved glucose tolerance in older mice not by altering the concentration of insulin. Cell growth was affected in ANGPTL8/betatrophin knockout HepG2. Based on UPLC-MS/MS, compared with wild type insulin-resistant HepG2 cells, we identified 83 differential metabolites in ANGPTL8/betatrophin knockout HepG2 cells after high insulin induction. Among the 14 differential up-regulated metabolites, D-mannose had the highest fold change. In insulin-resistant HepG2 cells, ANGPTL8/betatrophin knockout exerted an effect on the amino acid metabolism, carbohydrate metabolism, metabolism of cofactors and vitamins, lipid metabolism, nucleotide metabolism, and genetic information processing pathway. Conclusion:This study identified the effect of ANGPTL8/betatrophin on glucose tolerance in mice of different ages and metabolic profiles in insulin-resistant HepG2 cells. These findings may contribute to a new understanding of its role in glucose metabolism in the context of insulin resistance.

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Section: Introductionmentioning

confidence: 99%

ANGPTL8/Betatrophin Improves Glucose Tolerance in Older Mice and Metabolomic Analysis Reveals Its Role in Insulin Resistance in HepG2 Cells

Xu¹,

Wang²,

Li³

et al. 2021

DMSO

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“…ANGPTL-4 is a glycoprotein [25,26] that is involved in angiogenesis, lipid metabolism, and inflammation [27]. Particularly in CNS diseases, increased ANGPTL-4 reduces macrophage and microglia clearance of damaged myelin [28,29].…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid in Classical Trigeminal Neuralgia: An Exploratory Study on Candidate Biomarkers

et al. 2022

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Trigeminal neuralgia (TN) is a severe type of facial pain. A neurovascular conflict between cranial nerve V and a nearby vessel is the main pathophysiological mechanism, but additional factors are likely necessary to elicit TN. In this study, the primary aim was to explore differences in protein expression in the cerebrospinal fluid (CSF) of TN patients in relation to controls. Methods: Sixteen TN patients treated with microvascular decompression and 16 control patients undergoing spinal anesthesia for urological conditions were included. Lumbar CSF was collected preoperatively for the TN patients and before spinal anesthesia for the controls. A multiplexed proximity extension analysis of 91 CSF proteins was conducted using Proseek Multiplex Development 96, including biomarkers of cell communication, cell death, neurogenesis, and inflammation Results: The TN patients and the controls were of similar age, sex, and burden of co-morbidities. The TN patients exhibited higher concentrations of Clec11a, LGMN, MFG-E8, and ANGPTL-4 in CSF than the controls (q < 0.05). Conclusions: TN patients exhibited increased CSF biomarkers indicative of peripheral demyelinating injury (Clec11a), immune tolerance and destruction of myelin (LGMN), neuronal cell death (MFG-E8), and disturbances in myelin clearance (ANGPTL-8). Our findings are hypothesis-generating for candidate biomarkers and pathophysiological processes in classical TN.

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“…The role of ANGPTL proteins in glucose and lipid metabolism and in cancer has been investigated intensively [ 86 , 87 , 88 ]. Certain ANGPTL proteins are promising pharmacological targets for hypertriglyceridemia [ 89 ], but the role of these proteins in ovine pregnancy toxemia requires further investigation.…”

Section: Lipid Metabolism-related Molecular Mechanisms In Pregnancy T...mentioning

confidence: 99%

Pregnancy Toxemia in Ewes: A Review of Molecular Metabolic Mechanisms and Management Strategies

Liu

Ding

et al. 2023

Metabolites

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Pregnancy toxemia is a nutritional metabolic disease during late gestation in small ruminants. The condition is characterized by disorders in carbohydrate and fat metabolism. Obese and multiparous ewes are particularly susceptible to pregnancy toxemia, which may lead to maternal death, abortion, or premature birth. Highly productive multiparous meat ewes are major breeding animals, which has led to an increased incidence of the disease. However, the pathogenesis of pregnancy toxemia remains unclear and adequate disease prevention and treatment strategies are absent. Investigating the pathogenesis of pregnancy toxemia, especially the metabolic pathways of hepatic lipids, is key to an improved understanding of the condition. This review provides a snapshot of the genes that are associated with lipid metabolism in the ovine liver, including genes involved in fatty acid oxidation, acetyl coenzyme metabolism, and triglyceride synthesis; describes the interrelationships between these genes; and summarizes the diagnosis, prevention, and treatment of pregnancy toxemia.

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Emerging roles of angiopoietin‐like proteins in inflammation: Mechanisms and potential as pharmacological targets

Cited by 21 publications

References 152 publications

ANGPTL8/Betatrophin Improves Glucose Tolerance in Older Mice and Metabolomic Analysis Reveals Its Role in Insulin Resistance in HepG2 Cells

ANGPTL8/Betatrophin Improves Glucose Tolerance in Older Mice and Metabolomic Analysis Reveals Its Role in Insulin Resistance in HepG2 Cells

Cerebrospinal Fluid in Classical Trigeminal Neuralgia: An Exploratory Study on Candidate Biomarkers

Pregnancy Toxemia in Ewes: A Review of Molecular Metabolic Mechanisms and Management Strategies

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