The role of DGAT1 and DGAT2 in regulating tumor cell growth and their potential clinical implications

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 18, 2024

Abstract Lipid metabolism is widely reprogrammed in tumor cells. droplet a common organelle existing most mammal cells, and its complex dynamic functions maintaining redox metabolic balance, regulating endoplasmic reticulum stress, modulating chemoresistance, providing essential biomolecules ATP have been well established The balance between lipid formation catabolism critical to energy while the process of affects various for growth. imbalance synthesis fatty acids cells leads alteration content Diacylglycerol acyltransferase 1 diacylglycerol 2, enzymes that catalyze final step triglyceride synthesis, participate droplets regulation cell proliferation, migration invasion, prognosis tumor. Several 2 inhibitors developed over past decade shown anti-tumor effects preclinical models improvement clinical trials. In this review, we highlight key features acid different paradigms activities on migration, tumor, with hope these scientific findings will potential implications.

Language: Английский

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Bioengineering of Soybean Oil and Its Impact on Agronomic Traits

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2256 - 2256

Published: Jan. 23, 2023

Soybean is a major oil crop and also dominant source of nutritional protein. The 20% seed content (SOC) soybean much lower than that in most crops the fatty acid composition its native cannot meet specifications for some applications food industrial sectors. Considerable effort has been expended on bioengineering to tailor profiles improve SOC. Although significant advancements have made, such as creation high-oleic high-SOC soybean, those genetic modifications negative impacts production, instance, impaired germination or low protein content. In this review, we focus recent advances effects agronomic traits.

Language: Английский

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Progress in understanding and improving oil content and quality in seeds

Frontiers in Plant Science, Journal Year: 2023, Volume and Issue: 14

Published: Jan. 26, 2023

The world's population is projected to increase by two billion 2050, resulting in food and energy insecurity. Oilseed crops have been identified as key address these challenges: they produce store lipids the seeds triacylglycerols that can serve a source of food/feed, renewable fuels, other industrially-relevant chemicals. Therefore, improving seed oil content composition has generated immense interest. Research efforts aiming unravel regulatory pathways involved fatty acid synthesis identify targets for metabolic engineering made tremendous progress. This review provides summary current knowledge metabolism discusses how photochemical activity unconventional contribute high carbon conversion efficiency seeds. It also highlights importance

Language: Английский

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Identification of triacylglycerol remodeling mechanism to synthesize unusual fatty acid containing oils

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 26, 2024

Abstract Typical plant membranes and storage lipids are comprised of five common fatty acids yet over 450 unusual accumulate in seed oils various species. Plant important human animal nutrients, while some such as hydroxylated (HFA) used the chemical industry (lubricants, paints, polymers, cosmetics, etc.). Most extracted from non-agronomic crops leading to high production costs. Attempts engineer HFA into unsuccessful due bottlenecks overlapping pathways oil membrane lipid synthesis where not compatible. Physaria fendleri naturally overcomes these through a triacylglycerol (TAG) remodeling mechanism incorporated TAG after initial synthesis. involves unique lipase two diacylglycerol acyltransferases (DGAT) that selective for different stereochemical acyl-containing species within synthesis, partial degradation, resynthesis cycle. The interacts with DGAT1, localizes endoplasmic reticulum (with DGATs) puncta around droplet, likely forming metabolon near droplet-ER junction. Each characterized DGAT can increase accumulation engineered oils.

Language: Английский

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Synthetic Lipid Biology

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Cells contain thousands of different lipids. Their rapid and redundant metabolism, dynamic movement, many interactions with other biomolecules have justly earned lipids a reputation as vexing class molecules to understand. Further, the cell's hydrophobic metabolites, assemble into supramolecular structures─most commonly bilayers, or membranes─from which they carry out myriad biological functions. Motivated by this daunting complexity, researchers across disciplines are bringing order seeming chaos membranes. Here, we formalize these efforts "synthetic lipid biology". Inspired idea, central synthetic biology, that our abilities understand build systems intimately connected, organize studies approaches numerous fields create, manipulate, analyze biomembranes. These include construction membranes from scratch using chemical chemoenzymatic synthesis, editing pre-existing optogenetics protein engineering, detection metabolism transport bioorthogonal chemistry, probing lipid–protein membrane biophysical properties. What emerges is portrait an incipient field where chemists, biologists, physicists, engineers work together in proximity─like themselves─to clearer description properties, behaviors, functions

Language: Английский

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Human transmembrane protein 68 links triacylglycerol synthesis to membrane lipid homeostasis

FEBS Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Transmembrane protein 68 (TMEM68) is a recently identified mammalian triacylglycerol (TAG) synthase with high expression in the brain. How TMEM68 regulates cellular lipid metabolism concert other enzymatic pathways remains poorly understood. In this study, we assessed function neuro‐ and glioblastoma cells by combining genetic gain‐ loss‐of‐function approaches lipidomics. We found that promotes TAG synthesis droplet formation independently of canonical acyl‐CoA:diacylglycerol acyltransferase (DGAT) 1 2 enzymes contributes discrete fraction basal storage. Notably, overexpression increased storage lipids at expense membrane lipids, leading to profound reduction ether‐linked glycerophospholipids (GPLs). Moreover, altered levels were associated diminished prevalence polyunsaturated GPLs. conclude TMEM68, besides its function, acts as multifaceted regulator composition fatty acid homeostasis.

Language: Английский

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Triacylglycerol uptake and handling by macrophages: From fatty acids to lipoproteins

Progress in Lipid Research, Journal Year: 2023, Volume and Issue: 92, P. 101250 - 101250

Published: Aug. 22, 2023

Macrophages are essential innate immune cells and form our first line of defense. Also known as professional phagocytes, macrophages interact take up various particles, including lipids. Defective lipid handling can drive excessive accumulation leading to foam cell formation, a key feature cardiometabolic conditions such atherosclerosis, non-alcoholic fatty liver disease, obesity. At the same time, intracellular storage formation also be viewed protective anti-lipotoxic mechanism against lipid-rich environment associated elevated uptake. Traditionally, has primarily been linked cholesterol uptake via native modified low-density lipoproteins. However, other lipids, non-esterified acids triacylglycerol (TAG)-rich lipoproteins (very chylomicrons), with macrophages. Recent studies have identified multiple pathways mediating TAG processing by macrophages, endocytosis receptor/transporter-mediated internalization transport. This review will present current knowledge how different lipids lipoprotein particles address TAG-rich processed intracellularly. Understanding process species is necessary design future therapeutic interventions correct co-morbidities.

Language: Английский

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Genome-wide characterization of the GPAT gene family in bean (Phaseolus vulgaris L.) and expression analysis under abiotic stress and melatonin

Genetic Resources and Crop Evolution, Journal Year: 2024, Volume and Issue: 71(8), P. 4549 - 4569

Published: March 7, 2024

Abstract GPAT (sn-Glycerol-3-phosphate-1-O-acyltransferase) is a key enzyme in the biosynthesis of membrane lipids. Two kinds GPATs are involved production glycerolipids. While sn-1- s responsible for creating lysophosphatidic acid, sn-2- generate monoacylglycerol. genes beans ( Phaseolus vulgaris ) have never been investigated before. This study aimed to assess expression profiles common bean leaves under drought and salt stress apply bioinformatics tools genome-wide analysis gene family members. In P. genome, PvGPAT with molecular weights ranging from 50.2 60.4 kDa, amino acid counts 376 539, theoretical isoelectric points 8.41 9.46, instability indices 31.84 51.38 were found. Based on structure analysis, expected number exons introns was between 2 12. The proteins Arabidopsis thaliana , Glycine max Vitis vinifera Cicer arietinum Lens culinaris analyzed phylogenetically. G. A. evolutionarily related those beans. PvGPAT4/PvGPAT10 PvGPAT7/PvGPAT12 pairs detected be segmentally duplicated. this work, qRT-PCR performed six genes, effects salt, drought, melatonin treatments studied. role response at level. findings present will shed light members provide insight future functional research.

Language: Английский

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Towards Lipid from Microalgae: Products, Biosynthesis, and Genetic Engineering

Life, Journal Year: 2024, Volume and Issue: 14(4), P. 447 - 447

Published: March 28, 2024

Microalgae can convert carbon dioxide into organic matter through photosynthesis. Thus, they are considered as an environment-friendly and efficient cell chassis for biologically active metabolites. Microalgal lipids a class of compounds that be used raw materials food, feed, cosmetics, healthcare products, bioenergy, etc., with tremendous potential commercialization. In this review, we summarized the commercial lipid products from eukaryotic microalgae, updated mechanisms synthesis in microalgae. Moreover, reviewed enhancement lipids, triglycerides, polyunsaturated fatty acids, pigments, terpenes microalgae via environmental induction and/or metabolic engineering past five years. Collectively, provided comprehensive overview biosynthesis, induced strategies genetic microalgal lipids. Meanwhile, outlook has been presented development industries, emphasizing significance accurate analysis bioactivity, well high-throughput screening specific

Language: Английский

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Lipid metabolism regulation by dietary polysaccharides with different structural properties

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 270, P. 132253 - 132253

Published: May 13, 2024

Language: Английский

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