EDEM3 Modulates Plasma Triglyceride Level through Its Regulation of LRP1 Expression

Xu, Yuxin; Peloso, Gina M.; Nagai, Taylor H.; Mizoguchi, Taiji; Deik, Amy; Bullock, Kevin; Lin, Honghuang; Musunuru, Kiran; Yang, Qiong; Vasan, Ramachandran S.; Gerszten, Robert E.; Clish, Clary B.; Rader, Daniel J.; Kathiresan, Sekar

doi:10.1016/j.isci.2020.100973

Cited by 10 publications

(2 citation statements)

References 50 publications

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“…Similar observations were made on other LPLexpressing cells, including cardiomyocytes and macrophages (47). Hepatocyte-specific ER degradation enhancing alphamannosidase-like protein 3 (EDEM3) knockdown mice had increased LRP1 expression leading to enhanced VLDL uptake, thereby reducing plasma TG levels (48). Concurrently, data obtained from Gan et al (49) showed that ischemic heartderived small extracellular vesicles (sEVs) carrying miR-23-27-24 suppress adiponectin biosynthesis by downregulating EDEM3.…”

Section: Erad Factors' Involvement In Lipid Metabolismmentioning

confidence: 64%

The multifaceted roles of ER and Golgi in metabolic cardiomyopathy

Raja

Fonseka

Ganenthiran

et al. 2022

Front. Cardiovasc. Med.

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Metabolic cardiomyopathy is a significant global financial and health challenge; however, pathophysiological mechanisms governing this entity remain poorly understood. Among the main features of metabolic cardiomyopathy, the changes to cellular lipid metabolism have been studied and targeted for the discovery of novel treatment strategies obtaining contrasting results. The endoplasmic reticulum (ER) and Golgi apparatus (GA) carry out protein modification, sorting, and secretion activities that are more commonly studied from the perspective of protein quality control; however, they also drive the maintenance of lipid homeostasis. In response to metabolic stress, ER and GA regulate the expression of genes involved in cardiac lipid biogenesis and participate in lipid droplet formation and degradation. Due to the varied roles these organelles play, this review will focus on recapitulating the alterations and crosstalk between ER, GA, and lipid metabolism in cardiac metabolic syndrome.

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Section: Erad Factors' Involvement In Lipid Metabolismmentioning

confidence: 64%

The multifaceted roles of ER and Golgi in metabolic cardiomyopathy

Raja

Fonseka

Ganenthiran

et al. 2022

Front. Cardiovasc. Med.

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“…For instance, defective LDLR/LRP1-driven metabolic pathways might lead to decreased clearance of TGs. Expression and stability of LDLR and LRP1 in the liver might be affected by naturally occurring genetic variants (Oldoni et al, 2018;Paththinige et al, 2018;Reyes-Soffer et al, 2019;Xu et al, 2020). Moreover, it has been shown in mice that a high-fat diet can lead to the down-regulated expression of hepatic LRP1 by causing hyperglycemia with a high level of plasma triglycerides (Kim et al, 2014).…”

Section: Associations Between Apo-ciii Sialylation and Lipid Markersmentioning

confidence: 99%

Large-Scale Analysis of Apolipoprotein CIII Glycosylation by Ultrahigh Resolution Mass Spectrometry

et al. 2021

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Apolipoprotein-CIII (apo-CIII) is a glycoprotein involved in lipid metabolism and its levels are associated with cardiovascular disease risk. Apo-CIII sialylation is associated with improved plasma triglyceride levels and its glycosylation may have an effect on the clearance of triglyceride-rich lipoproteins by directing these particles to different metabolic pathways. Large-scale sample cohort studies are required to fully elucidate the role of apo-CIII glycosylation in lipid metabolism and associated cardiovascular disease. In this study, we revisited a high-throughput workflow for the analysis of intact apo-CIII by ultrahigh-resolution MALDI FT-ICR MS. The workflow includes a chemical oxidation step to reduce methionine oxidation heterogeneity and spectrum complexity. Sinapinic acid matrix was used to minimize the loss of sialic acids upon MALDI. MassyTools software was used to standardize and automate MS data processing and quality control. This method was applied on 771 plasma samples from individuals without diabetes allowing for an evaluation of the expression levels of apo-CIII glycoforms against a panel of lipid biomarkers demonstrating the validity of the method. Our study supports the hypothesis that triglyceride clearance may be regulated, or at least strongly influenced by apo-CIII sialylation. Interestingly, the association of apo-CIII glycoforms with triglyceride levels was found to be largely independent of body mass index. Due to its precision and throughput, the new workflow will allow studying the role of apo-CIII in the regulation of lipid metabolism in various disease settings.

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Multi-omics methods and tools in dissecting the oncovirus behavior in human host

Ahmed¹,

Veerabathiran²,

Sudhan³

et al. 2023

Oncogenic Viruses

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EDEM3 Modulates Plasma Triglyceride Level through Its Regulation of LRP1 Expression

Abstract: HIGHLIGHTSGenetic deficiency of EDEM3 leads to lower blood triglyceride (TG) level EDEM3 deficiency increases VLDL uptake by up-regulating LRP1 receptor expression Blood TG changes due to EDEM3 mutation correlate with the TG profile of EDEM3 KO cells

Cited by 10 publications

References 50 publications

The multifaceted roles of ER and Golgi in metabolic cardiomyopathy

The multifaceted roles of ER and Golgi in metabolic cardiomyopathy

Large-Scale Analysis of Apolipoprotein CIII Glycosylation by Ultrahigh Resolution Mass Spectrometry

Multi-omics methods and tools in dissecting the oncovirus behavior in human host

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