Increased Reticulon 3 (RTN3) Leads to Obesity and Hypertriglyceridemia by Interacting With Heat Shock Protein Family A (Hsp70) Member 5 (HSPA5)

Xiang, Rong; Fan, Liang‐Liang; Huang, Hao; Chen, Yaqin; He, Wanxia; Guo, Shanchun; Li, Jingjing; Jin, Jie‐Yuan; Du, Ran; Yan, Riqiang; Xia, Kun

doi:10.1161/circulationaha.117.030718

Cited by 31 publications

(51 citation statements)

References 41 publications

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“…Several lipid loci also harbored genes previously known to be involved in lipid metabolism. For example, a number of genes involved in NAFLD‐related traits like estrogen‐related receptor alpha ( Esrra ) (B'Chir et al , 2018), reticulon 3 ( Rtn3 ) (Xiang et al , 2018), and proprotein convertase subtilisin/kexin type 5 ( Pcsk5 ) (Iatan et al , 2009) were all located within loci for various liver TAGs and exhibited a local eQTL where the cis component of the expression correlated with the lipid (Dataset EV7). In total, we identified 76 loci whose cis component of gene expression was correlated with lipid levels (55 unique lipid species) as listed in Dataset EV7.…”

Section: Resultsmentioning

confidence: 99%

Genetic regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosis

Norheim

Krishnan

Bjellaas

et al. 2021

Molecular Systems Biology

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To elucidate the contributions of specific lipid species to metabolic traits, we integrated global hepatic lipid data with other omics measures and genetic data from a cohort of about 100 diverse inbred strains of mice fed a high-fat/high-sucrose diet for 8 weeks. Association mapping, correlation, structure analyses, and network modeling revealed pathways and genes underlying these interactions. In particular, our studies lead to the identification of Ifi203 and Map2k6 as regulators of hepatic phosphatidylcholine homeostasis and triacylglycerol accumulation, respectively. Our analyses highlight mechanisms for how genetic variation in hepatic lipidome can be linked to physiological and molecular phenotypes, such as microbiota composition.

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Section: Resultsmentioning

confidence: 99%

Genetic regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosis

Norheim

Krishnan

Bjellaas

et al. 2021

Molecular Systems Biology

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“…Expression of the HSPA8 ( 158 ) and CKB ( 159 ) were correlated with disease grades of hypertension, but these genes might be novel target for obesity. Recent studies have proposed that HSPA5 ( 160 ), YWHAH ( 161 ), ESR1 ( 162 ), PTEN ( 163 ), IRAK1 ( 164 ), CYR61 ( 165 ) and ZBTB16 ( 166 ) are involved in obesity. Previous reports demonstrate that SPTAN1 ( 167 ), STEAP2 ( 168 ), NEK6 ( 169 ), ARRB1 ( 170 ), FBXO11 ( 171 ), UBR2 ( 172 ), INTS6 ( 173 ), CDK14 ( 174 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Pathways and Genes in Obesity Using Bioinformatics Analysis and Molecular Docking Studies

Joshi

Vastrad²,

Joshi

et al. 2021

Front. Endocrinol.

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Obesity is an excess accumulation of body fat. Its progression rate has remained high in recent years. Therefore, the aim of this study was to diagnose important differentially expressed genes (DEGs) associated in its development, which may be used as novel biomarkers or potential therapeutic targets for obesity. The gene expression profile of E-MTAB-6728 was downloaded from the database. After screening DEGs in each ArrayExpress dataset, we further used the robust rank aggregation method to diagnose 876 significant DEGs including 438 up regulated and 438 down regulated genes. Functional enrichment analysis was performed. These DEGs were shown to be significantly enriched in different obesity related pathways and GO functions. Then protein–protein interaction network, target genes - miRNA regulatory network and target genes - TF regulatory network were constructed and analyzed. The module analysis was performed based on the whole PPI network. We finally filtered out STAT3, CORO1C, SERPINH1, MVP, ITGB5, PCM1, SIRT1, EEF1G, PTEN and RPS2 hub genes. Hub genes were validated by ICH analysis, receiver operating curve (ROC) analysis and RT-PCR. Finally a molecular docking study was performed to find small drug molecules. The robust DEGs linked with the development of obesity were screened through the expression profile, and integrated bioinformatics analysis was conducted. Our study provides reliable molecular biomarkers for screening and diagnosis, prognosis as well as novel therapeutic targets for obesity.

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“…Commonly, increased LDL-c and TG were recognized as the crucial risk factors of ASCVD ( Fernandez et al, 2015 ). Mutations of the pathogenic genes related to hypercholesterolemia and hypertriglyceridemia probably cause AS ( Surendran et al, 2012 ; Xiang et al, 2017 , 2018 ). Although reducing LDL-c levels has been proved to be an effective therapy, some patients still remain a high risk of ASCVD.…”

Section: Discussionmentioning

confidence: 99%

“…Dyslipidemia is a multi-factorial disease, which derives from complex interactions between genetic and environmental lesions. Many genes have been identified may be responsible for hypercholesterolemia and hypertriglyceridemia, for instance, Low-Density Lipoprotein Receptor , Proprotein Convertase Subtilisin/Kexin type 9 , Lipoprotein lipase , Apolipoprotein C2 , Reticulon 3 and et al ( Surendran et al, 2012 ; Xiang et al, 2017 , 2018 ). Low levels of HDL-c increase the risk of atherosclerotic cardiovascular disorder and shorten life expectancy.…”

Section: Introductionmentioning

confidence: 99%

A Novel Nonsense Mutation of ABCA8 in a Han-Chinese Family With ASCVD Leads to the Reduction of HDL-c Levels

et al. 2020

Self Cite

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Arteriosclerotic cardiovascular disease (ASCVD) is one of the major causes of death worldwide and most commonly develops as a result of atherosclerosis (AS). As we all know, dyslipidemia is a leading pathogenic risk factor for ASCVD, which leads to cardiac ischemic injury and myocardial infarction. Dyslipidemias include hypercholesterolemia, hypertriglyceridemia, increased low-density lipoprotein cholesterol (LDL-c) and decreased high density lipoproteins cholesterol (HDL-c). Mutations of dyslipidemia related genes have been proved to be the crucial contributor to the development of AS and ASCVD. In this study, a Han-Chinese family with ASCVD was enrolled and the lipid testing discovered an obvious reduced levels of HDL-c in the affected members. We then performed whole exome sequencing to detect the candidate genes of the family. After data filtering, a novel heterozygous nonsense mutation (NM_007168: c.3460C>T; p.R1154X) of ABCA8 was detected and validated to be co-separated in the family members by Sanger sequencing. Previous studies have proved that deleterious heterozygous ABCA8 variants may disrupt cholesterol efflux and reduce HDL-c levels in humans and mice. This study may be the second report related to ABCA8 mutations in patients with reduced levels of HDL-c. Our study not only contributed to the genetic counseling and prenatal genetic diagnosis of patients with ASCVD caused by reduced HDL-c levels, but also provided a new sight among ABCA8, cholesterol efflux and HDL-c levels.

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Increased Reticulon 3 (RTN3) Leads to Obesity and Hypertriglyceridemia by Interacting With Heat Shock Protein Family A (Hsp70) Member 5 (HSPA5)

Abstract: This study provides evidence for a role of RTN3 in inducing obesity and triglyceride accumulation and suggests that inhibiting the expression of RTN3 in fat tissue may be a novel therapeutic approach to treat obesity and hypertriglyceridemia.

Cited by 31 publications

References 41 publications

Genetic regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosis

Genetic regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosis

Identification of Key Pathways and Genes in Obesity Using Bioinformatics Analysis and Molecular Docking Studies

A Novel Nonsense Mutation of ABCA8 in a Han-Chinese Family With ASCVD Leads to the Reduction of HDL-c Levels

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