Angiopoietin-like protein 4 promotes hyperlipidemia-induced renal injury by down-regulating the expression of ACTN4

Li, Yue; Gong, Wangqiu; Liu, Jing; Chen, Xingxing; Suo, Yanhong; Yang, Huabing; Gao, Xia

doi:10.1016/j.bbrc.2022.01.061

Cited by 9 publications

(6 citation statements)

References 26 publications

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“…The experimental method was as described previously [ 10 ]. The primary antibodies were angiopoietin-like 3 polyclonal antibody (Abcam, Cambridge, UK, ab126718), ACTN4 monoclonal antibody (Abcam, Cambridge, UK, ab108198), podocin antibody (Abcam, Cambridge, UK, ab229037) and anti-CD2AP antibody (Sigma‒Aldrich, MO, USA, HPA003267).…”

Section: Methodsmentioning

confidence: 99%

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ANGPTL3 is involved in kidney injury in high-fat diet-fed mice by suppressing ACTN4 expression

Wang

et al. 2022

Lipids Health Dis

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Objective We wanted to explore how angiopoietin-like 3 (ANGPTL3) impact hyperlipidemia-induced renal injury. Methods ANGPTL3 knockout mice and wild-type C57 mice were set up in four groups (N = 5) depending on a normal or 60% high-fat diet: wild-type with normal diet (WT), angptl3-/- with normal diet (KO), wild-type + high-fat diet (WT + HF) and angptl3-/- + high-fat diet (KO + HF). The detection time points were the 9th, 13th, 17th and 21st weeks after modeling. Serum lipid and urinary protein levels of mice in each group were detected, and pathological changes in the kidney were analyzed. Moreover, the expression of ANGPTL3, α-actinin-4 (ACTN4), CD2-associated protein (CD2AP) and podocin was tested in the glomerulus by immunohistochemistry (IHC). Results In the WT + HF group, hyperlipidemia and proteinuria could be observed at the 9th week and were gradually aggravated with time. Compared with WT + HF mice, the levels of serum lipids and proteinuria in KO + HF mice were significantly reduced, and the width of podocyte foot processes (FPs) fusion was also markedly improved. The IHC results suggested that in WT + HF mice, the expression of ANGPTL3 was significantly enhanced. After modeling, ACTN4 expression was markedly weakened in the glomeruli of WT + HF mice. Different to WT mice, ACTN4 expression was not observed obviously change in KO + HF mice. Compared with the normal diet group, the expression of podocin showed a decline in WT mice treated with high-fat diet and showed a significant difference from the 17th week. In addition, podocin expression in KO + HF glomeruli was also found to be weak but not significantly different from that in WT + HF glomeruli at the four time points. The expression of CD2AP showed similar results among the four groups. Conclusion ANGPTL3 could play a role in the mechanism of hyperlipidemia-associated podocyte injury via ACTN4.

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Section: Methodsmentioning

confidence: 99%

“…The analysis method refers to a previous article [ 10 ]. In brief, the IHC results were analyzed semiquantitatively using ImageJ 1.50.…”

Section: Methodsmentioning

confidence: 99%

ANGPTL3 is involved in kidney injury in high-fat diet-fed mice by suppressing ACTN4 expression

Wang

et al. 2022

Lipids Health Dis

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“…In addition, CYP7A1 overexpression in the luteoloside intervention group was consistent with a significant increase in its enzymatic activity in the liver tissue. Angiopoietin-like protein 4 (Angptl4) is a key gene in the regulation of lipid and glucose metabolism ( 38 ), and hyperlipidemia levels were significantly reduced in Angptl4 knockout mice ( 39 ). The results of this study showed that compared with the control group, the expression of Angptl4 in liver tissues was downregulated after luteoloside intervention, but the difference was not statistically significant, indicating that Angptl4 may not be a key gene in the mechanism of luteolin lowering blood lipid.…”

Section: Discussionmentioning

confidence: 99%

The hypolipidemic mechanism of chrysanthemum flavonoids and its main components, luteolin and luteoloside, based on the gene expression profile

et al. 2022

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In this study, the following four groups of mice with hyperlipidemia were involved: the model control group (MC), the Chrysanthemum flavonoids group (CF), the luteolin group, and the luteoloside group. The whole gene expression profile was detected in the liver tissues of each group. Differential genes significantly enriched in the biological process of gene ontology (GO) items and Kyoto Encyclopedia of Genes and Genomes (KEGG) were selected, and 4 differential genes related to lipid metabolism were selected for further real-time quantitative PCR verification. Compared with the MC, 41 differential genes such as Sqle, Gck, and Idi1 were screened in the CF intervention group; 68 differential genes such as Acsl3, Cyp7a1, and Lpin1 were screened in the luteolin intervention group (CF); and 51 differential genes such as Acaca, Cyp7a1, and Lpin1 were screened in the luteoloside group. The mechanism of CF to improve hyperlipidemia is very complex, mainly involving biological processes such as cholesterol and fatty acid metabolism and glycolysis, luteolin mainly involves the synthesis and transport of cholesterol, and luteoloside mainly involves fatty acid metabolism. The functional pathways of CF may not be completely the same as luteolin and luteoloside, and further study is needed on the mechanism of action of other components.

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“…In the normal diet group, lipids, proteins and carbohydrates account for 10%, 20%, and 70% of the total calories, respectively ( Jiang et al, 2020 ). In a high-fat diet, fat, protein and carbohydrate account for 60%, 15%, and 25% respectively ( Li et al, 2022b ). In animal models, even a diet containing 1% cholesterol has been shown to induce kidney damage ( Ding et al, 2022 ).…”

Section: Survey Methodologymentioning

confidence: 99%

“…In animal models, a high fat diet also causes lipid deposition in kidney tissues in a short period of time. Li et al (2022b) studied mice with a high fat diet for 21 weeks, and selected four-time nodes at nine, 13, 17 and 21 weeks. Their results showed that, compared with the normal diet group, the plasma TC and TG in the HFD group had significantly increased on the ninth week.…”

Section: Survey Methodologymentioning

confidence: 99%

The role of exercise in improving hyperlipidemia-renal injuries induced by a high-fat diet: a literature review

Chen

Xie

Hong

2023

PeerJ

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A diet that is high in sugar and fat is a precursor to various chronic diseases, especially hyperlipidemia. Patients with hyperlipidemia have increased levels of plasma free fatty acids and an ectopic accumulation of lipids. The kidney is one of the main organs affected by this disease and, recently, there have been more studies conducted on renal injury caused by hyperlipidemia. The main pathological mechanism is closely related to renal lipotoxicity. However, in different kidney cells, the reaction mechanism varies due to the different affinities of the lipid receptors. At present, it is believed that in addition to lipotoxicity, hyperlipidemia induced-renal injury is also closely related to oxidative stress, endoplasmic reticulum stress, and inflammatory reactions, which are the result of multiple factors. Exercise plays an important role in the prevention of various chronic diseases and recently emerging researches indicated its positive effects to renal injury caused by hyperlipidemia. However, there are few studies summarizing the effects of exercise on this disease and the specific mechanisms need to be further explored. This article summarizes the mechanisms of hyperlipidemia induced-renal injury at the cellular level and discusses the ways in which exercise may regulate it. The results provide theoretical support and novel approaches for identifying the intervention target to treat hyperlipidemia induced-renal injury.

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Angiopoietin-like protein 4 promotes hyperlipidemia-induced renal injury by down-regulating the expression of ACTN4

Cited by 9 publications

References 26 publications

ANGPTL3 is involved in kidney injury in high-fat diet-fed mice by suppressing ACTN4 expression

ANGPTL3 is involved in kidney injury in high-fat diet-fed mice by suppressing ACTN4 expression

The hypolipidemic mechanism of chrysanthemum flavonoids and its main components, luteolin and luteoloside, based on the gene expression profile

The role of exercise in improving hyperlipidemia-renal injuries induced by a high-fat diet: a literature review

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