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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927470 | PMC |
| http://dx.doi.org/10.1194/jlr.M040089 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Direct cytosol delivery of mRNA by micron-sized co-assembly with designer oligopeptides.
J Mater Chem B
January 2025
Chemical and Biological Engineering Department, The Hong Kong University of Science and Technology, Hong Kong SAR, China.
Inefficient endosomal escape has been regarded as the main bottleneck for intracellular nucleic acid delivery. While most research efforts have been spent on designing various nano-sized particles, we took a different path here, investigating micron-sized carriers for direct cytosol entry. Using the spontaneous co-assembly of mRNA and the designer 27 amino acid oligopeptide named pepMAX2, micron-sized co-assemblies were obtained with various sizes by altering the concentration of NaCl salt and time for pre-incubation.
View Article and Find Full Text PDFThe Golgi apparatus is a critical organelle responsible for intracellular trafficking and signaling, orchestrating essential processes such as protein and lipid sorting . Dysregulation of its function has been implicated in various pathologies, including obesity, diabetes, and cancer, highlighting its importance as a potential therapeutic target. Despite this, the development of tools to selectively target the Golgi in specific cell types remain a significant unmet challenge in imaging and drug discovery.
View Article and Find Full Text PDFAdministration of AICAR, an AMPK Activator, Prevents and Reverses Diabetic Polyneuropathy (DPN) by Regulating Mitophagy.
Int J Mol Sci
December 2024
Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes in both Type 1 (T1D) and Type 2 (T2D). While there are no specific medications to prevent or treat DPN, certain strategies can help halt its progression. In T1D, maintaining tight glycemic control through insulin therapy can effectively prevent or delay the onset of DPN.
View Article and Find Full Text PDFα/β hydrolase domain-containing protein 1 acts as a lysolipid lipase and is involved in lipid droplet formation.
Natl Sci Rev
December 2024
Aix Marseille Univ, CEA, CNRS, Institute of Bioscience and Biotechnology of Aix Marseille, BIAM, Saint-Paul-Lez-Durance 13108, France.
Lipid droplets (LDs) are the major sites of lipid and energy homeostasis. However, few LD biogenesis proteins have been identified. Using model microalga , we show that ABHD1, an α/β-hydrolase domain-containing protein, is localized to the LD surface and stimulates LD formation through two actions: one enzymatic and one structural.
View Article and Find Full Text PDFA complete assembly and annotation of the American shad genome yields insights into the origins of diadromy.
Genome Biol Evol
December 2024
Cornell University, Department of Natural Resources and the Environment, Ithaca, NY.
Transitions across ecological boundaries, such as those separating freshwater from the sea, are major drivers of phenotypic innovation and biodiversity. Despite their importance to evolutionary history, we know little about the mechanisms by which such transitions are accomplished. To help shed light on these mechanisms, we generated the first high-quality, near-complete assembly and annotation of the genome of the American shad (Alosa sapidissima), an ancestrally diadromous (migratory between salinities) fish in the order Clupeiformes of major cultural and historical significance.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!