Zebrafish as an Emerging Model for Dyslipidemia and Associated Diseases

Ka, Jun; Jin, Suk‐Won

doi:10.12997/jla.2021.10.1.42

Cited by 22 publications

(20 citation statements)

References 75 publications

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“…Zebrafish is considered a valuable model species to understand abnormalities in lipid metabolism that result in disease progression. Fundamental lipoprotein pathways are conserved in humans and zebrafish ( 31 ) and adult zebrafish fed a cholesterol-rich diet are highly susceptible to hypercholesterolemia ( 32 , 33 ). This model also allowed us to test the therapeutic potential of two dietary components which can eventually be considered as hypercholesterolemia-controlling agents in humans ( 34 ).…”

Section: Introductionmentioning

confidence: 99%

Management of Hypercholesterolemia Through Dietary ß-glucans–Insights From a Zebrafish Model

et al. 2022

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Consumption of lipid-rich foods can increase the blood cholesterol content. β-glucans have hypocholesterolemic effect. However, subtle changes in their molecular branching can influence bioactivity. Therefore, a comparative investigation of the cholesterol-lowering potential of two β-glucans with different branching patterns and a cholesterol-lowering drug, namely simvastatin was undertaken employing the zebrafish (Danio rerio) model of diet-induced hypercholesterolemia. Fish were allocated to 5 dietary treatments; a control group, a high cholesterol group, two β-glucan groups, and a simvastatin group. We investigated plasma total cholesterol, LDL and HDL cholesterol levels, histological changes in the tissues, and explored intestinal transcriptomic changes induced by the experimental diets. Dietary cholesterol likely caused the suppression of endogenous cholesterol biosynthesis, induced dysfunction of endoplasmic reticulum and mitochondria, and altered the histomorphology of the intestine. The two β-glucans and simvastatin significantly abated the rise in plasma cholesterol levels and restored the expression of specific genes to alleviate the endoplasmic reticulum-related effects induced by the dietary cholesterol. Furthermore, the distinct patterns of transcriptomic changes in the intestine elicited by the oat and microalga β-glucans impacted processes such as fatty acid metabolism, protein catabolic processes, and nuclear division. Oat and microalgal β-glucans also altered the pattern of lipid deposition in the liver. Our study provides insights into the effectiveness of different β-glucans to alleviate dysfunctions in lipid metabolism caused by dietary cholesterol.

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Section: Introductionmentioning

confidence: 99%

Management of Hypercholesterolemia Through Dietary ß-glucans–Insights From a Zebrafish Model

et al. 2022

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“…Apart from these physiological similarities, zebrafish also possess orthologues of critical lipid metabolic genes including microsomal TG transfer protein ( mttp ), fatty acid transport protein ( slc27a ), and acyl-CoA synthetase ( acsl ) gene families, as well as the LDL receptor ( ldlr ). In addition, the expression pattern of these genes appear to be comparable to humans [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

A Novel 2-Hit Zebrafish Model to Study Early Pathogenesis of Non-Alcoholic Fatty Liver Disease

et al. 2022

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Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in adults. NAFLD progresses from benign liver fat accumulation to liver inflammation and cirrhosis, and ultimately leads to liver failure. Although several rodent models have been established for studying NAFLD, they have limitations that include cost, speed of disease development, key dissimilarities, and poor amenability to pharmacological screens. Here, we present a novel 2-hit zebrafish model to replicate aspects of NAFLD pathogenesis. We fed zebrafish larvae a high-fat diet (HFD) to drive liver fat accumulation (first hit). Next, we exacerbated liver-specific inflammation using a transgenic line (fabp10-CETI-PIC3) that induces the expression of proinflammatory cytokines following induction with doxycycline (second hit). These hits promoted fat accumulation and liver inflammation, as demonstrated by the high expression of inflammatory cytokines, macrophage infiltration, stress induction, and hepatic lipid droplet accumulation. Furthermore, zebrafish in this paradigm showed deranged glucose metabolism. To validate a small-molecule screening approach, we treated HFD-fed fish with pioglitazone, a drug shown to be beneficial for NAFLD in humans, and measured a sharp reduction in liver lipid accumulation. These results demonstrate new utility for zebrafish in modeling early NAFLD pathogenesis and demonstrate their feasibility for in vivo screening of new pharmacological interventions.

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“…In mammals changes in lipid metabolism and increased lipid storage affected innate immunity and caused modifications in Tlr signaling, endocytosis, and cytokine secretion ( 74 , 75 ). In fact, dyslipidemia and other metabolic diseases in mammals are closely connected to an altered immune response ( 76 , 77 ). Taking into consideration the interaction between lipid metabolism and Tlr activity, these morphological/metabolic adaptations may explain the reduced Tlr repertoire in flatfish and D. mawsoni .…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor Evolution: Does Temperature Matter?

et al. 2022

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Toll-like receptors (TLRs) recognize conserved pathogen-associated molecular patterns (PAMPs) and are an ancient and well-conserved group of pattern recognition receptors (PRRs). The isolation of the Antarctic continent and its unique teleost fish and microbiota prompted the present investigation into Tlr evolution. Gene homologues of tlr members in teleosts from temperate regions were present in the genome of Antarctic Nototheniidae and the non-Antarctic sister lineage Bovichtidae. Overall, in Nototheniidae apart from D. mawsoni, no major tlr gene family expansion or contraction occurred. Instead, lineage and species-specific changes in the ectodomain and LRR of Tlrs occurred, particularly in the Tlr11 superfamily that is well represented in fish. Positive selective pressure and associated sequence modifications in the TLR ectodomain and within the leucine-rich repeats (LRR), important for pathogen recognition, occurred in Tlr5, Tlr8, Tlr13, Tlr21, Tlr22, and Tlr23 presumably associated with the unique Antarctic microbiota. Exposure to lipopolysaccharide (Escherichia coli O111:B4) Gram negative bacteria did not modify tlr gene expression in N. rossii head–kidney or anterior intestine, although increased water temperature (+4°C) had a significant effect.

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Zebrafish as an Emerging Model for Dyslipidemia and Associated Diseases

Cited by 22 publications

References 75 publications

Management of Hypercholesterolemia Through Dietary ß-glucans–Insights From a Zebrafish Model

Management of Hypercholesterolemia Through Dietary ß-glucans–Insights From a Zebrafish Model

A Novel 2-Hit Zebrafish Model to Study Early Pathogenesis of Non-Alcoholic Fatty Liver Disease

Toll-Like Receptor Evolution: Does Temperature Matter?

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