The acyl-CoA synthetase 4 (ACSL4) has been implicated in carcinogenesis and neuronal development. Acyl-CoA synthetases are essential enzymes of lipid metabolism, and ACSL4 is distinguished by its preference for arachidonic acid. Two human ACSL4 isoforms arising from differential splicing were analyzed by ectopic expression in COS cells. We found that the ACSL4_v1 variant localized to the inner side of the plasma membrane including microvilli, and was also present in the cytosol. ACSL4_v2 contains an additional N-terminal hydrophobic region; this isoform was located at the endoplasmic reticulum and on lipid droplets. A third isoform was designed de novo by appending a mitochondrial targeting signal. All three ACSL4 variants showed the same specific enzyme activity. Overexpression of the isoenzymes increased cellular uptake of arachidonate to the same degree, indicating that the metabolic trapping of fatty acids is independent of the subcellular localization. Remarkably, phospholipid metabolism was changed by ACSL4 expression. Labeling with arachidonate showed that the amount of newly synthesized phosphatidylinositol was increased by all three ACSL4 isoenzymes but not by ACSL1. This was dependent on the expression level and the localization of the ACSL4 isoform. We conclude that in our model system exogenous fatty acids are channeled preferentially towards phosphatidylinositol by ACSL4 overexpression. The differential localization of the endogenous isoenzymes may provide compartment specific precursors of this anionic phospholipid important for many signaling processes.
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http://dx.doi.org/10.1016/j.bbalip.2013.10.018 | DOI Listing |
Curr Opin Allergy Clin Immunol
February 2025
Division of Allergic Diseases, Mayo Clinic Rochester, Rochester, Minnesota, USA.
Purpose Of Review: Mast cell activation is defined by activation of mast cells by varying stimuli with release of chemical mediators either through degranulation or release of de novo synthesized proteins or lipid mediators. Currently, tryptase measurement increase during symptomatic episodes is the most accepted biomarker measurement for mast cell activation. However, newer diagnostic tools including clinically available urinary mast cell mediators are noninvasive and can be more readily obtained compared to serum tryptase levels.
View Article and Find Full Text PDFMol Omics
January 2025
Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, Punjab, India.
The present work aimed to examine the primary mechanisms of liver damage, namely the impact of gut-derived endotoxins along the gut-liver axis and adipose-derived free fatty acids along the adipose-liver axis. These processes are known to play a significant role in the development of hepatic inflammation and steatosis. Although possible overlapping in the pathogenesis was expected, these processes have unique pathophysiological consequences.
View Article and Find Full Text PDFWorld J Orthop
December 2024
Department of Orthopaedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, São Paulo, Brazil.
The gut microbiome, a complex ecosystem of microorganisms in the digestive tract, has emerged as a critical factor in human health, influencing metabolic, immune, and neurological functions. This review explores the connection between the gut microbiome and orthopedic health, examining how gut microbes impact bone density, joint integrity, and skeletal health. It highlights mechanisms linking gut dysbiosis to inflammation in conditions such as rheumatoid arthritis and osteoarthritis, suggesting microbiome modulation as a potential therapeutic strategy.
View Article and Find Full Text PDFFront Vet Sci
December 2024
College of Animal Science and Technology, Ningxia University, Yinchuan, China.
Introduction: Postpartum dairy cows are susceptible to negative energy balance caused by decreased feed intake and the initiation of lactation. Sijunzi San, a famous Chinese traditional herbal formulation, can promote gastrointestinal digestion and absorption and improve disorders of intestinal microbiota. Therefore, we hypothesized that Sijunzi San might alleviate negative energy balance in postpartum dairy cows by modulating the structure of the rumen microbiota and enhancing its fermentation capacity.
View Article and Find Full Text PDFFront Vet Sci
December 2024
Institute of Dairy and Animal Sciences, University of Agriculture, Faisalabad, Pakistan.
Introduction: High-producing dairy cows often face calving stress and reduced feed intake during the transition period, leading to body fat mobilization to meet production demands. Supplementing rations with energy-dense sources like rumen-protected glucose (RPG) may enhance production performance in early lactation.
Methods: This study evaluated the effects of RPG supplementation on feed intake, body condition score (BCS), production performance, and blood metabolites in 32 early-lactation Holstein Friesian cows (6 ± 1 DIM; milk yield: 30 ± 5 kg/day; body weight: 550 ± 50 kg; BCS: 3.
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