ArticleJournal of lipid research2014
Hepatic trans-Golgi action coordinated by the GTPase ARFRP1 is crucial for lipoprotein lipidation and assembly.
Article in Journal of lipid research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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8 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- A Bayesian hierarchically structured prior for gene-based association testing with multiple traits in genome-wide association studies.Genetic epidemiology · 2022Pooled it
- Rab30 facilitates lipid homeostasis during fasting.Nature communications · 2024Article
- Targeted Proteomic Analysis of Small GTPases in Radioresistant Breast Cancer Cells.Analytical chemistry · 2022Article
- QTL-mapping in the obese Berlin Fat Mouse identifies additional candidate genes for obesity and fatty liver disease.Scientific reports · 2022Article
- miR-146a regulates insulin sensitivity via NPR3.Cellular and molecular life sciences : CMLS · 2021Article
- Effect of single nucleotide polymorphisms on intramuscular fat content in Hungarian Simmental cattle.Asian-Australasian journal of animal sciences · 2018Article
- Bioinformatics analysis of microRNAs related to blood stasis syndrome in diabetes mellitus patients.Bioscience reports · 2018Article
- The beneficial effects of empagliflozin, an SGLT2 inhibitor, on atherosclerosis in ApoEDiabetologia · 2017Article
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Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The liver is a major organ in whole body lipid metabolism and malfunctioning can lead to various diseases including dyslipidemia, fatty liver disease, and type 2 diabetes. Triglycerides and cholesteryl esters are packed in the liver as very low density lipoproteins (VLDLs). Generation of these lipoproteins is initiated in the endoplasmic reticulum and further maturation likely occurs in the Golgi. ADP-ribosylation factor-related protein 1 (ARFRP1) is a small trans-Golgi-associated guanosine triphosphatase (GTPase) that regulates protein sorting and is required for chylomicron lipidation and assembly in the intestine. Here we show that the hepatocyte-specific deletion of Arfrp1 (Arfrp1(liv-/-)) results in impaired VLDL lipidation leading to reduced plasma triglyceride levels in the fasted state as well as after inhibition of lipoprotein lipase activity by Triton WR-1339. In addition, the concentration of ApoC3 that comprises 40% of protein mass of secreted VLDLs is markedly reduced in the plasma of Arfrp1(liv-/-) mice but accumulates in the liver accompanied by elevated triglycerides. Fractionation of Arfrp1(liv-/-) liver homogenates reveals more ApoB48 and a lower concentration of triglycerides in the Golgi compartments than in the corresponding fractions from control livers. In conclusion, ARFRP1 and the Golgi apparatus play an important role in lipoprotein maturation in the liver by influencing lipidation and assembly of proteins to the lipid particles.
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