Establishment of a lipid metabolism disorder model in ApoEb mutant zebrafish

The health risks associated with glyphosate (GLY) have recently received increasing attention. However, its potential vascular toxic effects in occupationally exposed populations remain unclear. This study assessed the effects of GLY on human aortic vascular smooth muscle cells (HAVSMCs) and the relationship between GLY and atherosclerosis. The results demonstrate that GLY induces a relatively larger and more flattened cell morphology, which is typical of cellular senescence and promotes senescence-associated β-galactosidase activity, as well as the expression of p53, p21, and p16 proteins in HAVSMCs. Regarding toxic effects, GLY induces the accumulation of reactive oxygen species, DNA damage, and mitochondrial damage in HAVSMCs. Mechanistically, the nuclear factor erythroid 2-related factor 2–Kelch-like ECH-associated protein 1 pathway is activated in response to oxidative stress produced by GLY. In an in vivo model, GLY led to dyslipidemia and macrophage recruitment in zebrafish vasculature. In conclusion, our results demonstrate that GLY induces vascular toxicity and may be a potential risk for atherosclerosis. These findings highlight the need for concern about cardiovascular risk in occupational populations chronically exposed to GLY.

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“…The analysis of lipid levels was performed as previously described . Briefly, 50 larvae were homogenized in PBS by ultrasonic fragmentation.…”

Section: Methodsmentioning

confidence: 99%

Glyphosate Causes Vascular Toxicity through Cellular Senescence and Lipid Accumulation

Zhang

Wang

et al. 2023

Chem. Res. Toxicol.

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“…Simvastin, ezetimibe and Xuezhikang reduced the recruitment of neutrophils and macrophages. [ 149 ] Zebrafish model of Atherosclerosis Zebrafish larvae fed with high cholesterol diet and lipopolysaccharide Develop efficient model of atherosclerosis for high-throughput screening of drugs Formation of plaques in the zebrafish blood vessels containing fibrous tissue and lipids. Increased severity when induced with both high cholesterol diet and lipopolysaccharide compared to individual treatment.…”

Section: Zebrafish Models To Investigate Therapeutics Against Chronic...mentioning

confidence: 99%

A review on current advancement in zebrafish models to study chronic inflammatory diseases and their therapeutic targets

Balde,

Ramya,

Nazeer

2024

Heliyon

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“…147 A recent study showed that mutants for apoEb exhibit increased lipid disposition in the vasculature after being fed a high-fat diet. 148 When treated with simvastatin, this effect was mitigated. While no further investigation of the mechanism was described, this is an exciting finding since apoEb was suspected to be involved in nonlipid transport functions (eg, modulation of cytoskeletal assembly 149 ) due to its widespread expression.…”

Section: Lipoprotein Metabolism In Circulationmentioning

confidence: 99%

Zebrafish ApoB-Containing Lipoprotein Metabolism: A Closer Look

Moll,

Farber

2024

ATVB

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Zebrafish have become a powerful model of mammalian lipoprotein metabolism and lipid cell biology. Most key proteins involved in lipid metabolism, including cholesteryl ester transfer protein, are conserved in zebrafish. Consequently, zebrafish exhibit a human-like lipoprotein profile. Zebrafish with mutations in genes linked to human metabolic diseases often mimic the human phenotype. Zebrafish larvae develop rapidly and externally around the maternally deposited yolk. Recent work revealed that any disturbance of lipoprotein formation leads to the accumulation of cytoplasmic lipid droplets and an opaque yolk, providing a visible phenotype to investigate disturbances of the lipoprotein pathway, already leading to discoveries in microsomal triglyceride transfer protein and ApoB (apolipoprotein B). By 5 days of development, the digestive system is functional, making it possible to study fluorescently labeled lipid uptake in the transparent larvae. These and other approaches enabled the first in vivo description of the STAB (stabilin) receptors, showing lipoprotein uptake in endothelial cells. Various zebrafish models have been developed to mimic human diseases by mutating genes known to influence lipoproteins (eg, ldlra , apoC2 ). This review aims to discuss the most recent research in the zebrafish ApoB-containing lipoprotein and lipid metabolism field. We also summarize new insights into lipid processing within the yolk cell and how changes in lipid flux alter yolk opacity. This curious new finding, coupled with the development of several techniques, can be deployed to identify new players in lipoprotein research directly relevant to human disease.

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Establishment of a lipid metabolism disorder model in ApoEb mutant zebrafish

Cited by 8 publications

References 53 publications

Glyphosate Causes Vascular Toxicity through Cellular Senescence and Lipid Accumulation

Glyphosate Causes Vascular Toxicity through Cellular Senescence and Lipid Accumulation

A review on current advancement in zebrafish models to study chronic inflammatory diseases and their therapeutic targets

Zebrafish ApoB-Containing Lipoprotein Metabolism: A Closer Look

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