Mice Fed a High‐Cholesterol Diet Supplemented with Quercetin‐3‐Glucoside Show Attenuated Hyperlipidemia and Hyperinsulinemia Associated with Differential Regulation of PCSK9 and LDLR in their Liver and Pancreas

Mbikay, Majambu; Mayne, Janice; Sirois, Francine; Fedoryak, Olesya; Raymond, Angela; Noad, Jennifer; Chrétien, Michel

doi:10.1002/mnfr.201700729

Cited by 35 publications

(30 citation statements)

References 59 publications

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“…Additionally, Q3G is reported to be as effective as quercetin in ameliorating insulin resistance by regulating the insulin receptor substrate 1 (IRS-1) function of the endothelium [43]. Isoquercetin, otherwise known as quercetin-O-beta-glucoside, is supplemented to a high cholesterol diet that could regulate expression and secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9), reversing the hyperlipidemia and hyperinsulinemia caused by the diet [44]. In accordance with the previous and present works, these studies have shown that cooperatively the antioxidant and anti-diabetic effects of LSE may be attributed to their biological activities of the flavonoids components.…”

Section: Discussionmentioning

confidence: 99%

Flavonoids Identification and Pancreatic Beta-Cell Protective Effect of Lotus Seedpod

et al. 2020

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Oxidative stress is highly associated with the development of diabetes mellitus (DM), especially pancreatic beta-cell injury. Flavonoids derived from plants have caused important attention in the prevention or treatment of DM. Lotus seedpod belongs to a traditional Chinese herbal medicine and has been indicated to possess antioxidant, anti-age, anti-glycative, and hepatoprotective activities. The purpose of this study was to demonstrate the pancreatic beta-cell protective effects of lotus seedpod aqueous extracts (LSE) against oxidative injury. According to HPLC/ESI-MS-MS method, LSE was confirmed to have flavonoids derivatives, especially quercetin-3-glucuronide (Q3G). In vitro, LSE dose-dependently improved the survival and function of rat pancreatic beta-cells (RIN-m5F) from hydrogen peroxide (H2O2)-mediated loss of cell viability, impairment of insulin secretion, and promotion of oxidative stress. LSE showed potential in decreasing the H2O2-induced occurrence of apoptosis. In addition, H2O2-triggered acidic vesicular organelle formation and microtubule-associated protein light chain 3 (LC3)-II upregulation, markers of autophagy, were increased by LSE. Molecular data explored that antiapoptotic and autophagic effects of LSE, comparable to that of Q3G, might receptively be mediated via phospho-Bcl-2-associated death promoter (p-Bad)/B-cell lymphoma 2 (Bcl-2) and class III phosphatidylinositol-3 kinase (PI3K)/LC3-II signal pathway. In vivo, LSE improved the DM symptoms and pancreatic cell injury better than metformin, a drug that is routinely prescribed to treat DM. These data implied that LSE induces the autophagic signaling, leading to protect beta-cells from oxidative stress-related apoptosis and injury.

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Section: Discussionmentioning

confidence: 99%

Flavonoids Identification and Pancreatic Beta-Cell Protective Effect of Lotus Seedpod

et al. 2020

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“…Quercetin-3-glucoside, a glucoside form of quercetin, can alleviate hyperlipidemia and hyperinsulinemia in mice fed a high-cholesterol diet (Mbikay et al, 2018). Moreover, quercetin contributes to alleviating male reproductive toxicity caused by environmental factors.…”

Section: Discussionmentioning

confidence: 99%

Quercetin Affects Spermatogenesis-Related Genes of Mouse Exposed to High-Cholesterol Diet

Yang

Bae

Song

et al. 2020

J Anim Reprod Biotechnol

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A high-cholesterol diet can reduce male fertility. However, it is not known whether a high-cholesterol diet can regulate the expression of genes involved in sperm maturation and sperm fertilizing ability. Quercetin, a natural product, is known to have cytoprotective effects by regulating lipid metabolism in various cell types. This study aimed to confirm the expression of genes involved in sperm maturation in the testes of mice fed a high-cholesterol diet and to determine whether quercetin can reverse the genetic regulation of cholesterol. Mice were divided into groups fed a normal chow diet and a high-cholesterol diet. Mice fed the high-cholesterol diet were dose-dependently supplemented with quercetin for 6 weeks. Investigations using quantitative PCR and in situ hybridization revealed that the high-cholesterol diet alters the expression of genes associated with sperm maturation in the testes of mice, and this was reversed with the supplementation of quercetin. In addition, the high-cholesterol diet regulated the expression of genes related to lipid metabolism in the liver of mice. Under a highcholesterol diet, quercetin can improve male fertility by regulating the expression of genes involved in sperm maturation.

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“…The target miRNAs of circRNA_0049392 are miR-7037-5p and miR-6919-5p, which have been validated as a receptor of low-density lipoprotein (LDL). LDL receptor encoded by Ldlr gene allows the degradation of LDL [15]. A study conducted by Kelli et al, in 2017 [16] have re ected the attenuated disease development, decreased triglycerides accumulation and decreased in ammation responses in Ldlr-/mice fed with HFD.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA Expression Profiles and Features in NAFLD Mice: A Study Using RNA-Seq Data

Yuan

Diao

et al. 2020

Preprint

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Background: Nonalcoholic fatty liver disease (NAFLD) is primarily characterized by the hepatic cholesterol accumulation. Circular RNA (circRNA), one of noncoding RNA, involves in many liver diseases progression. However, no recent studies on circRNA expression profiles in NAFLD have been reported previously.Methods: A NAFLD mouse model was constructed by providing high-fat diet (HFD) for 32 weeks. The circRNAs expression profile in normal mice and NAFLD mice were determined using high-output RNA sequencing method and bioinformatics methods, while the differentially expressed circRNAs were confirmed using Sanger sequencing and qRT-PCR. The circRNA-miRNA network was also predicted. The biological functions of circRNAs were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).Results: The results demonstrated the successful construction of NAFLD mice model by immunohistology and serology assay. In total, 93 dysregulated circRNAs were observed, including 57 upregulated circRNAs and 36 downregulated circRNAs, in the NAFLD group. The circRNA-miRNA network revealed the complex interaction between circRNAs and its potential miRNA targets in NAFLD. The characteristic of tissue-specific expression in circRNA was demonstrated. The differentially expressed circRNAs with important biological function were also annotated using GO and KEGG. Both DDAH1 and VAV3 genes were found to be associated with the NAFLD development.Conclusions: Taken together, this study demonstrated the circRNAs expression profile and features in NAFLD, which may provide potential biological markers for the pathogenesis of NAFLD.

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Mice Fed a High‐Cholesterol Diet Supplemented with Quercetin‐3‐Glucoside Show Attenuated Hyperlipidemia and Hyperinsulinemia Associated with Differential Regulation of PCSK9 and LDLR in their Liver and Pancreas

Abstract: In mice, dietary Q3G could counter HCD-induced hyperlipidemia and hyperinsulinemia, in part by oppositely modulating hepatic and pancreatic PCSK9 secretion.

Cited by 35 publications

References 59 publications

Flavonoids Identification and Pancreatic Beta-Cell Protective Effect of Lotus Seedpod

Flavonoids Identification and Pancreatic Beta-Cell Protective Effect of Lotus Seedpod

Quercetin Affects Spermatogenesis-Related Genes of Mouse Exposed to High-Cholesterol Diet

Circular RNA Expression Profiles and Features in NAFLD Mice: A Study Using RNA-Seq Data

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