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Keywords = lysophosphatidic acid acyltransferase

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26 pages, 1989 KiB  
Review
The Role of the AGPAT2 Gene in Adipose Tissue Biology and Congenital Generalized Lipodystrophy Pathophysiology
by Maria Eduarda Cardoso de Melo, Letícia Marques Gomes da Silva, Ana Carolina Costa Cavalcante, Josivan Gomes Lima and Julliane Tamara Araújo de Melo Campos
Int. J. Mol. Sci. 2025, 26(11), 5416; https://doi.org/10.3390/ijms26115416 - 5 Jun 2025
Viewed by 667
Abstract
1-Acylglycerol-3-phosphate O-acyltransferase (1-AGPAT) is an enzyme family composed of 11 isoforms. Notably, 1-AGPAT 2, the most studied isoform since its discovery, is a critical enzyme in the triglyceride synthesis pathway, converting lysophosphatidic acid to phosphatidic acid. In addition, AGPAT2 gene expression is shown [...] Read more.
1-Acylglycerol-3-phosphate O-acyltransferase (1-AGPAT) is an enzyme family composed of 11 isoforms. Notably, 1-AGPAT 2, the most studied isoform since its discovery, is a critical enzyme in the triglyceride synthesis pathway, converting lysophosphatidic acid to phosphatidic acid. In addition, AGPAT2 gene expression is shown to be essential for adipocyte development and maturation. Defects in AGPAT2 are responsible for significant pathophysiological alterations related to adipose tissue (AT). Pathogenic variants in this gene are the molecular etiology of Congenital Generalized Lipodystrophy type 1 (CGL1), in which fatty tissue is absent from birth. Metabolically, these individuals have several metabolic complications, including hypoleptinemia, hypoadiponectinemia, hyperglycemia, and hypertriglyceridemia. Furthermore, numerous AGPAT2 pathogenic variants that enormously affect the amino acid sequence, the tertiary structure of 1-AGPAT 2, and their transmembrane and functional domains were found in CGL1 patients. However, studies investigating the genotype–phenotype relationship in this disease are scarce. Here, we used bioinformatics tools to verify the effect of the main pathogenic variants reported in the AGPAT2 gene: c.366-588del, c.589-2A>G, c.646A>T, c.570C>A, c.369-372delGCTC, c.202C>T, c.514G>A, and c.144C>A in the 1-AGPAT 2 membrane topology. We also correlated the phenotype of CGL1 subjects harboring these variants to understand the genotype–phenotype relationship. We provided an integrative view of clinical, genetic, and metabolic features from CGL1 individuals, helping to understand the role of 1-AGPAT 2 in the pathogenesis of this rare disease. Data reviewed here highlight the importance of new molecular studies to improve our knowledge concerning clinical and genetic heterogeneity in CGL1. Full article
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21 pages, 6232 KiB  
Article
Genome-Wide Association Analysis Identifies Candidate Loci for Callus Induction in Rice (Oryza sativa L.)
by Wintai Kamolsukyeunyong, Yeetoh Dabbhadatta, Aornpilin Jaiprasert, Burin Thunnom, Wasin Poncheewin, Samart Wanchana, Vinitchan Ruanjaichon, Theerayut Toojinda and Parichart Burns
Plants 2024, 13(15), 2112; https://doi.org/10.3390/plants13152112 - 30 Jul 2024
Cited by 1 | Viewed by 2081
Abstract
Callus induction (CI) is a critical trait for transforming desirable genes in plants. A genome-wide association study (GWAS) analysis was conducted on the rice germplasms of 110 Indica rice accessions, in which three tissue culture media, B5, MS, and N6, were used for [...] Read more.
Callus induction (CI) is a critical trait for transforming desirable genes in plants. A genome-wide association study (GWAS) analysis was conducted on the rice germplasms of 110 Indica rice accessions, in which three tissue culture media, B5, MS, and N6, were used for the CI of those rice panels’ mature seeds. Seven quantitative trait loci (QTLs) on rice chromosomes 2, 6, 7, and 11 affected the CI percentage in the three media. For the B5 medium, one QTL (qCI–B5–Chr6) was identified on rice chromosome 6; for the MS medium, two QTLs were identified on rice chromosomes 2 and 6 (qCI–MS–Chr2 and qCI–MS–Chr6, respectively); for the N6 medium, four QTLs were identified on rice chromosomes 6, 7, and 11 (qCI–N6–Chr6.1 and qCI–N6–Chr6.2, qCI–N6–Chr7, and qCI–N6–Chr11, respectively). Fifty-five genes were identified within the haplotype blocks corresponding to these QTLs, thirty-one of which showed haplotypes associated with different CI percentages in those media. qCI–B5–Chr6 was located in the same region as qCI–N6–Chr6.2, and the Caleosin-related family protein was also identified in this region. Analysis of the gene-based haplotype revealed the association of this gene with different CI percentages in both B5 and N6 media, suggesting that the gene may play a critical role in the CI mechanism. Moreover, several genes, including those that encode the beta-tubulin protein, zinc finger protein, RNP–1 domain-containing protein, and lysophosphatidic acid acyltransferase, were associated with different CI percentages in the N6 medium. The results of this study provide insights into the potential QTLs and candidate genes for callus induction in rice that contribute to our understanding of the physiological and biochemical processes involved in callus formation, which is an essential tool in the molecular breeding of rice. Full article
(This article belongs to the Special Issue Plant Tissue Culture and Plant Regeneration)
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25 pages, 8381 KiB  
Article
PfbZIP85 Transcription Factor Mediates ω-3 Fatty Acid-Enriched Oil Biosynthesis by Down-Regulating PfLPAT1B Gene Expression in Plant Tissues
by Xusheng Huang, Yali Zhou, Xianfei Shi, Jing Wen, Yan Sun, Shuwei Chen, Ting Hu, Runzhi Li, Jiping Wang and Xiaoyun Jia
Int. J. Mol. Sci. 2024, 25(8), 4375; https://doi.org/10.3390/ijms25084375 - 16 Apr 2024
Cited by 6 | Viewed by 1987
Abstract
The basic leucine zipper (bZIP) transcription factor (TF) family is one of the biggest TF families identified so far in the plant kingdom, functioning in diverse biological processes including plant growth and development, signal transduction, and stress responses. For Perilla frutescens, a [...] Read more.
The basic leucine zipper (bZIP) transcription factor (TF) family is one of the biggest TF families identified so far in the plant kingdom, functioning in diverse biological processes including plant growth and development, signal transduction, and stress responses. For Perilla frutescens, a novel oilseed crop abundant in polyunsaturated fatty acids (PUFAs) (especially α-linolenic acid, ALA), the identification and biological functions of bZIP members remain limited. In this study, 101 PfbZIPs were identified in the perilla genome and classified into eleven distinct groups (Groups A, B, C, D, E, F, G, H, I, S, and UC) based on their phylogenetic relationships and gene structures. These PfbZIP genes were distributed unevenly across 18 chromosomes, with 83 pairs of them being segmental duplication genes. Moreover, 78 and 148 pairs of orthologous bZIP genes were detected between perilla and Arabidopsis or sesame, respectively. PfbZIP members belonging to the same subgroup exhibited highly conserved gene structures and functional domains, although significant differences were detected between groups. RNA-seq and RT-qPCR analysis revealed differential expressions of 101 PfbZIP genes during perilla seed development, with several PfbZIPs exhibiting significant correlations with the key oil-related genes. Y1H and GUS activity assays evidenced that PfbZIP85 downregulated the expression of the PfLPAT1B gene by physical interaction with the promoter. PfLPAT1B encodes a lysophosphatidate acyltransferase (LPAT), one of the key enzymes for triacylglycerol (TAG) assembly. Heterogeneous expression of PfbZIP85 significantly reduced the levels of TAG and UFAs (mainly C18:1 and C18:2) but enhanced C18:3 accumulation in both seeds and non-seed tissues in the transgenic tobacco lines. Furthermore, these transgenic tobacco plants showed no significantly adverse phenotype for other agronomic traits such as plant growth, thousand seed weight, and seed germination rate. Collectively, these findings offer valuable perspectives for understanding the functions of PfbZIPs in perilla, particularly in lipid metabolism, showing PfbZIP85 as a suitable target in plant genetic improvement for high-value vegetable oil production. Full article
(This article belongs to the Section Molecular Plant Sciences)
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10 pages, 865 KiB  
Article
The Specificities of Lysophosphatidic Acid Acyltransferase and Fatty Acid Desaturase Determine the High Content of Myristic and Myristoleic Acids in Cyanobacterium sp. IPPAS B-1200
by Alexander Y. Starikov, Roman A. Sidorov, Kirill S. Mironov and Dmitry A. Los
Int. J. Mol. Sci. 2024, 25(2), 774; https://doi.org/10.3390/ijms25020774 - 7 Jan 2024
Cited by 2 | Viewed by 1667
Abstract
The cyanobacterial strain Cyanobacterium sp. IPPAS B-1200 isolated from Lake Balkhash is characterized by high relative amounts of myristic (30%) and myristoleic (10%) acids. The remaining fatty acids (FAs) are represented mainly by palmitic (20%) and palmitoleic (40%) acids. We expressed the genes [...] Read more.
The cyanobacterial strain Cyanobacterium sp. IPPAS B-1200 isolated from Lake Balkhash is characterized by high relative amounts of myristic (30%) and myristoleic (10%) acids. The remaining fatty acids (FAs) are represented mainly by palmitic (20%) and palmitoleic (40%) acids. We expressed the genes for lysophosphatidic acid acyltransferase (LPAAT; EC 2.3.1.51) and Δ9 fatty acid desaturase (FAD; EC 1.14.19.1) from Cyanobacterium sp. IPPAS B-1200 in Synechococcus elongatus PCC 7942, which synthesizes myristic and myristoleic acids at the level of 0.5–1% and produces mainly palmitic (~60%) and palmitoleic (35%) acids. S. elongatus cells that expressed foreign LPAAT synthesized myristic acid at 26%, but did not produce myristoleic acid, suggesting that Δ9-FAD of S. elongatus cannot desaturate FAs with chain lengths less than C16. Synechococcus cells that co-expressed LPAAT and Δ9-FAD of Cyanobacterium synthesized up to 45% palmitoleic and 9% myristoleic acid, suggesting that Δ9-FAD of Cyanobacterium is capable of desaturating saturated acyl chains of any length. Full article
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16 pages, 7818 KiB  
Article
Role of Different Members of the AGPAT Gene Family in Milk Fat Synthesis in Bubalus bubalis
by Zhipeng Li, Ruijia Li, Honghe Ren, Chaobin Qin, Jie Su, Xinhui Song, Shuwan Wang, Qingyou Liu, Yang Liu and Kuiqing Cui
Genes 2023, 14(11), 2072; https://doi.org/10.3390/genes14112072 - 13 Nov 2023
Cited by 9 | Viewed by 2285
Abstract
During triacylglycerol synthesis, the acylglycerol-3-phosphate acyltransferase (AGPAT) family catalyzes the conversion of lysophosphatidic acid to phosphatidic acid and the acylation of sn-2 fatty acids. However, the catalytic activity of different AGPAT members is different. Therefore, this study aimed to investigate the mechanism through [...] Read more.
During triacylglycerol synthesis, the acylglycerol-3-phosphate acyltransferase (AGPAT) family catalyzes the conversion of lysophosphatidic acid to phosphatidic acid and the acylation of sn-2 fatty acids. However, the catalytic activity of different AGPAT members is different. Therefore, this study aimed to investigate the mechanism through which different AGPATs affect the efficiency of TAG synthesis and fatty acid composition. The conservation of amino acid sequences and protein domains of the AGPAT family was analyzed, and the functions of AGPAT1, AGPAT3, and AGPAT4 genes in buffalo mammary epithelial cells (BMECs) were studied using RNA interference and gene overexpression. Prediction of the protein tertiary structure of the AGPAT family demonstrated that four conservative motifs (motif1, motif2, motif3, and motif6) formed a hydrophobic pocket in AGPAT proteins, except AGPAT6. According to cytological studies, AGPAT1, AGPAT3, and AGPAT4 were found to promote the synthesis and fatty acid compositions of triacylglycerol, especially UFA compositions of triacylglycerol, by regulating ACSL1, FASN, GPAM, DGAT2, and PPARG gene expression. This study provides new insights into the role of different AGPAT gene family members involved in TAG synthesis, and a reference for improving the fatty acid composition of milk. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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23 pages, 11543 KiB  
Article
Multiplexed Host-Induced Gene Silencing of Aspergillus flavus Genes Confers Aflatoxin Resistance in Groundnut
by Kalyani Prasad, Kalenahalli Yogendra, Hemalatha Sanivarapu, Kanniah Rajasekaran, Jeffrey W. Cary, Kiran K. Sharma and Pooja Bhatnagar-Mathur
Toxins 2023, 15(5), 319; https://doi.org/10.3390/toxins15050319 - 5 May 2023
Cited by 16 | Viewed by 3797
Abstract
Aflatoxins are immunosuppressive and carcinogenic secondary metabolites, produced by the filamentous ascomycete Aspergillus flavus, that are hazardous to animal and human health. In this study, we show that multiplexed host-induced gene silencing (HIGS) of Aspergillus flavus genes essential for fungal sporulation and [...] Read more.
Aflatoxins are immunosuppressive and carcinogenic secondary metabolites, produced by the filamentous ascomycete Aspergillus flavus, that are hazardous to animal and human health. In this study, we show that multiplexed host-induced gene silencing (HIGS) of Aspergillus flavus genes essential for fungal sporulation and aflatoxin production (nsdC, veA, aflR, and aflM) confers enhanced resistance to Aspergillus infection and aflatoxin contamination in groundnut (<20 ppb). Comparative proteomic analysis of contrasting groundnut genotypes (WT and near-isogenic HIGS lines) supported a better understanding of the molecular processes underlying the induced resistance and identified several groundnut metabolites that might play a significant role in resistance to Aspergillus infection and aflatoxin contamination. Fungal differentiation and pathogenicity proteins, including calmodulin, transcriptional activator-HacA, kynurenine 3-monooxygenase 2, VeA, VelC, and several aflatoxin pathway biosynthetic enzymes, were downregulated in Aspergillus infecting the HIGS lines. Additionally, in the resistant HIGS lines, a number of host resistance proteins associated with fatty acid metabolism were strongly induced, including phosphatidylinositol phosphate kinase, lysophosphatidic acyltransferase-5, palmitoyl-monogalactosyldiacylglycerol Δ-7 desaturase, ceramide kinase-related protein, sphingolipid Δ-8 desaturase, and phospholipase-D. Combined, this knowledge can be used for groundnut pre-breeding and breeding programs to provide a safe and secure food supply. Full article
(This article belongs to the Section Mycotoxins)
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20 pages, 10614 KiB  
Article
Metabolic Composition and Quality Traits of Polygonatum cyrtonema Hua from Different Germplasms and Age Sections Based on Widely Targeted Metabolomics Analysis
by Qingshuang Wang, Jingjie Ban, Roudi Cai, Xueying Zhang, Chunwang Lai, Yan Chen, Xiaoli Li, Cuirong Chen, Yukun Chen, Zihao Zhang, Zhongxiong Lai and Yuling Lin
Int. J. Mol. Sci. 2023, 24(7), 6077; https://doi.org/10.3390/ijms24076077 - 23 Mar 2023
Cited by 15 | Viewed by 2488
Abstract
Polygonatum rhizomes are rich in various compounds with many biological activities and are widely used in functional foods and pharmaceutical products. In order to screen for superior Polygonatum cyrtonema Hua (P. cyrtonema) germplasm and also to elucidate the nutritional and medicinal values [...] Read more.
Polygonatum rhizomes are rich in various compounds with many biological activities and are widely used in functional foods and pharmaceutical products. In order to screen for superior Polygonatum cyrtonema Hua (P. cyrtonema) germplasm and also to elucidate the nutritional and medicinal values of rhizomes, the metabolic composition and quality traits of rhizomes from different germplasms and age sections of P. cyrtonema were analysed by widely targeted metabolomics, and the molecular mechanism of triacylglycerol synthesis was explored. The results showed that the different germplasms and age sections of P. cyrtonema were rich in different nutritional and medicinal components. Of these, the broad-leaved green stem (GK) germplasm is rich in polysaccharides, alkaloids, and lipids; the pointed-leaved green stem (JL) germplasm is rich in flavonoids, steroids, and amino acids, while the pointed-leaved purple stem (JZ) germplasm contains more phenolic acids. The one-year (AT) age section is rich in polysaccharides, steroids, organic acids, and lipids; the three years (CT) age section contains more flavonoids, alkaloids, and amino acid metabolites. Lipids were significantly enriched in the broad-leaved green stem germplasm and the one-year age section. Interestingly, the highest accumulation of triacylglycerols, an important component of lipids, was also found in the GK germplasm and the AT age section. Nineteen, 14, and 13 members of the glycerol-3-phosphate acyltransferase (GPAT), lysophosphatidic acid acyltransferase (LPAT), and diacylglycerol acyltransferase (DGAT) gene families, respectively, involved in triacylglycerol synthesis were also identified. The quantitative real-time PCR (qRT-PCR) results further suggested that the differentially expressed PcDGAT1, PcDGAT2.4, PcGPAT9.1, PcLPAT2.9, and PcLPAT4.3 genes may play important roles in triacylglycerol synthesis in P. cyrtonema. Therefore, this study provides a new theoretical reference for product development and the breeding of new varieties of Polygonatum species. Full article
(This article belongs to the Collection Feature Papers in Molecular Plant Sciences)
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24 pages, 5175 KiB  
Article
Longer Duration of Active Oil Biosynthesis during Seed Development Is Crucial for High Oil Yield—Lessons from Genome-Wide In Silico Mining and RNA-Seq Validation in Sesame
by Bhagwat Nawade, Ajay Kumar, Rasna Maurya, Rajkumar Subramani, Rashmi Yadav, Kuldeep Singh and Parimalan Rangan
Plants 2022, 11(21), 2980; https://doi.org/10.3390/plants11212980 - 4 Nov 2022
Cited by 8 | Viewed by 3221
Abstract
Sesame, one of the ancient oil crops, is an important oilseed due to its nutritionally rich seeds with high protein content. Genomic scale information for sesame has become available in the public databases in recent years. The genes and their families involved in [...] Read more.
Sesame, one of the ancient oil crops, is an important oilseed due to its nutritionally rich seeds with high protein content. Genomic scale information for sesame has become available in the public databases in recent years. The genes and their families involved in oil biosynthesis in sesame are less studied than in other oilseed crops. Therefore, we retrieved a total of 69 genes and their translated amino acid sequences, associated with gene families linked to the oil biosynthetic pathway. Genome-wide in silico mining helped identify key regulatory genes for oil biosynthesis, though the findings require functional validation. Comparing sequences of the SiSAD (stearoyl-acyl carrier protein (ACP)-desaturase) coding genes with known SADs helped identify two SiSAD family members that may be palmitoyl-ACP-specific. Based on homology with lysophosphatidic acid acyltransferase (LPAAT) sequences, an uncharacterized gene has been identified as SiLPAAT1. Identified key regulatory genes associated with high oil content were also validated using publicly available transcriptome datasets of genotypes contrasting for oil content at different developmental stages. Our study provides evidence that a longer duration of active oil biosynthesis is crucial for high oil accumulation during seed development. This underscores the importance of early onset of oil biosynthesis in developing seeds. Up-regulating, identified key regulatory genes of oil biosynthesis during early onset of seed development, should help increase oil yields. Full article
(This article belongs to the Special Issue Advances in Plants Lipid Metabolism)
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10 pages, 1392 KiB  
Article
Middle-Aged Lpaatδ-Deficient Mice Have Altered Metabolic Measures
by Michelle Victoria Tomczewski, Maria Fernanda Fernandes, Rajan Singh Grewal and Robin Elaine Duncan
Life 2022, 12(11), 1717; https://doi.org/10.3390/life12111717 - 27 Oct 2022
Cited by 1 | Viewed by 2017
Abstract
Lysophosphatidic acid acyltransferases/acylglycerophosphate acyltransferases (LPAATs/AGPATs) are a group of homologous enzymes that catalyze the formation of phosphatidic acid (PA) from lysophosphatidic acid. We have previously reported that LPAATδ/AGPAT4 localizes to mitochondria, suggesting a potential role in energy metabolism. However, in prior studies of [...] Read more.
Lysophosphatidic acid acyltransferases/acylglycerophosphate acyltransferases (LPAATs/AGPATs) are a group of homologous enzymes that catalyze the formation of phosphatidic acid (PA) from lysophosphatidic acid. We have previously reported that LPAATδ/AGPAT4 localizes to mitochondria, suggesting a potential role in energy metabolism. However, in prior studies of young Lpaatδ-deficient mice (age 9–12 weeks old), we found no differences in body weights, food intakes, activity levels, respiratory gas exchange, or energy expenditure compared to their wildtype (Wt) littermates. To test whether Lpaatδ−/− mice may develop differences in metabolic measures with advancing age, we recorded body weights and food intakes, and used metabolic chambers to assess ambulatory and locomotor activity levels, oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (RER), and total energy expenditure (heat). Fourteen-month-old Lpaatδ−/− mice had significantly lower mean body weights compared to Wt littermate controls (44.6 ± 1.08 g vs. 53.5 ± 0.42 g, respectively), but no significant differences in food intake or activity levels. This phenotypic difference was accompanied by significantly elevated 24 h daily, and 12 h light and dark photoperiod average VO2 (~20% higher) and VCO2 (~30% higher) measures, as well as higher RER and total energy expenditure (heat) values compared to Wt control littermates. Thus, an age-related metabolic phenotype is evident in Lpaatδ−/− mice. Future studies should examine the role of the lipid-modifying enzyme LPAATδ across the lifespan for greater insight into its role in normal and pathophysiology. Full article
(This article belongs to the Special Issue Advances in Mitochondrial Biology)
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19 pages, 4754 KiB  
Article
The Examination of the Role of Rice Lysophosphatidic Acid Acyltransferase 2 in Response to Salt and Drought Stresses
by Aamir Ali Shaikh, Alfatih Alamin, Chenxi Jia, Wei Gong, Xianjun Deng, Qingwen Shen and Yueyun Hong
Int. J. Mol. Sci. 2022, 23(17), 9796; https://doi.org/10.3390/ijms23179796 - 29 Aug 2022
Cited by 4 | Viewed by 2493
Abstract
Phosphatidic acid (PA) is an important signal molecule in various biological processes including osmotic stress. Lysophosphatidic acid acyltransferase (LPAT) acylates the sn-2 position of the glycerol backbone of lysophosphatidic acid (LPA) to produce PA. The role of LPAT2 and its PA in osmotic [...] Read more.
Phosphatidic acid (PA) is an important signal molecule in various biological processes including osmotic stress. Lysophosphatidic acid acyltransferase (LPAT) acylates the sn-2 position of the glycerol backbone of lysophosphatidic acid (LPA) to produce PA. The role of LPAT2 and its PA in osmotic stress response remains elusive in plants. Here we showed that LPAT2-derived PA is important for salt and drought stress tolerance in rice. Rice LPAT2 was localized to the endoplasmic reticulum (ER) to catalyze the PA synthesis. The LPAT2 transcript was induced by osmotic stress such as high salinity and water deficit. To reveal its role in osmotic stress response, an LPAT2 knockdown mutant, designated lpat2, was isolated from rice, which contained a reduced PA level relative to wild type (WT) plants under salt stress and water deficit. The lpat2 mutant was more susceptible to osmotic stress and less sensitive to abscisic acid (ABA) than that of WT, which was recovered by either PA supplementation or genetic LPAT2 complementation. Moreover, suppressed LPAT2 also led to a large number of differentially expressed genes (DEGs) involved in diverse processes, particularly, in ABA response, kinase signaling, and ion homeostasis in response to salt stress. Together, LPAT2-produced PA plays a positive role in osmotic tolerance through mediating ABA response, which leads to transcriptional alteration of genes related to ABA response, protein kinase signaling, and ion homeostasis. Full article
(This article belongs to the Special Issue Function and Metabolism of Plant Lipids)
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16 pages, 2173 KiB  
Review
Lipid Metabolism in Cancer: The Role of Acylglycerolphosphate Acyltransferases (AGPATs)
by Angeliki Karagiota, Georgia Chachami and Efrosyni Paraskeva
Cancers 2022, 14(1), 228; https://doi.org/10.3390/cancers14010228 - 4 Jan 2022
Cited by 22 | Viewed by 5337
Abstract
Altered lipid metabolism is an emerging hallmark of aggressive tumors, as rapidly proliferating cancer cells reprogram fatty acid (FA) uptake, synthesis, storage, and usage to meet their increased energy demands. Central to these adaptive changes, is the conversion of excess FA to neutral [...] Read more.
Altered lipid metabolism is an emerging hallmark of aggressive tumors, as rapidly proliferating cancer cells reprogram fatty acid (FA) uptake, synthesis, storage, and usage to meet their increased energy demands. Central to these adaptive changes, is the conversion of excess FA to neutral triacylglycerides (TAG) and their storage in lipid droplets (LDs). Acylglycerolphosphate acyltransferases (AGPATs), also known as lysophosphatidic acid acyltransferases (LPAATs), are a family of five enzymes that catalyze the conversion of lysophosphatidic acid (LPA) to phosphatidic acid (PA), the second step of the TAG biosynthesis pathway. PA, apart from its role as an intermediate in TAG synthesis, is also a precursor of glycerophospholipids and a cell signaling molecule. Although the different AGPAT isoforms catalyze the same reaction, they appear to have unique non-overlapping roles possibly determined by their distinct tissue expression and substrate specificity. This is best exemplified by the role of AGPAT2 in the development of type 1 congenital generalized lipodystrophy (CGL) and is also manifested by recent studies highlighting the involvement of AGPATs in the physiology and pathology of various tissues and organs. Importantly, AGPAT isoform expression has been shown to enhance proliferation and chemoresistance of cancer cells and correlates with increased risk of tumor development or aggressive phenotypes of several types of tumors. Full article
(This article belongs to the Special Issue Feature Paper from Journal Reviewers)
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14 pages, 1836 KiB  
Article
Identification of Transcription Factors and the Regulatory Genes Involved in Triacylglycerol Accumulation in the Unicellular Red Alga Cyanidioschyzon merolae
by Sota Takahashi, Riho Okubo, Yu Kanesaki, Baifeng Zhou, Kazuhiro Takaya, Satoru Watanabe, Kan Tanaka and Sousuke Imamura
Plants 2021, 10(5), 971; https://doi.org/10.3390/plants10050971 - 13 May 2021
Cited by 13 | Viewed by 3705
Abstract
Microalgal triacylglycerols (TAGs) are a good feedstock for liquid biofuel production. Improving the expression and/or function of transcription factors (TFs) involved in TAG accumulation may increase TAG content; however, information on microalgae is still lacking. In this study, 14 TFs in the unicellular [...] Read more.
Microalgal triacylglycerols (TAGs) are a good feedstock for liquid biofuel production. Improving the expression and/or function of transcription factors (TFs) involved in TAG accumulation may increase TAG content; however, information on microalgae is still lacking. In this study, 14 TFs in the unicellular red alga Cyanidioschyzon merolae were identified as candidate TFs regulating TAG accumulation using available transcriptome and phosphoproteome data under conditions driving TAG accumulation. To investigate the roles of these TFs, we constructed TF-overexpression strains and analyzed lipid droplet (LD) formation and TAG contents in the cells grown under standard conditions. Based on the results, we identified four TFs involved in LD and TAG accumulation. RNA-Seq analyses were performed to identify genes regulated by the four TFs using each overexpression strain. Among the TAG biosynthesis-related genes, only the gene encoding the endoplasmic reticulum-localized lysophosphatidic acid acyltransferase 1 (LPAT1) was notably increased among the overexpression strains. In the LPAT1 overexpression strain, TAG accumulation was significantly increased compared with the control strain under normal growth conditions. These results indicate that the four TFs positively regulate TAG accumulation by changing their target gene expression in C. merolae. Full article
(This article belongs to the Special Issue Algal Biomass)
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13 pages, 2558 KiB  
Article
Plastid Glycerol-3-phosphate Acyltransferase Enhanced Plant Growth and Prokaryotic Glycerolipid Synthesis in Brassica napus
by Huiling Kang, Chenxi Jia, Nian Liu, Alfatih Alamin Alhussain Aboagla, Wenling Chen, Wei Gong, Shaohua Tang and Yueyun Hong
Int. J. Mol. Sci. 2020, 21(15), 5325; https://doi.org/10.3390/ijms21155325 - 27 Jul 2020
Cited by 8 | Viewed by 3312
Abstract
Plastid-localized glycerol-3-phosphate acyltransferase (ATS1) catalyzes the first-step reaction in glycerolipid assembly through transferring an acyl moiety to glycerol-3-phosphate (G3P) to generate lysophosphatidic acid (LPA), an intermediate in lipid metabolism. The effect of ATS1 overexpression on glycerolipid metabolism and growth remained to be elucidated [...] Read more.
Plastid-localized glycerol-3-phosphate acyltransferase (ATS1) catalyzes the first-step reaction in glycerolipid assembly through transferring an acyl moiety to glycerol-3-phosphate (G3P) to generate lysophosphatidic acid (LPA), an intermediate in lipid metabolism. The effect of ATS1 overexpression on glycerolipid metabolism and growth remained to be elucidated in plants, particularly oil crop plants. Here, we found that overexpression of BnATS1 from Brassica napus enhanced plant growth and prokaryotic glycerolipid biosynthesis. BnATS1 is localized in chloroplasts and an in vitro assay showed that BnATS1 had acylation activity toward glycerol 3-phosphate to produce LPA. Lipid profiling showed that overexpression of BnATS1 led to increases in multiple glycerolipids including phosphatidylglycerol (PG), monogalactosyldiacylglycerol (MGDG), phosphatidylcholine (PC), and phosphatidylinositol (PI), with increased polyunsaturated fatty acids. Moreover, increased MGDG was attributed to the elevation of 34:6- and 34:5-MGDG, which were derived from the prokaryotic pathway. These results suggest that BnATS1 promotes accumulation of polyunsaturated fatty acids in cellular membranes, thus enhances plant growth under low-temperature conditions in Brassica napus. Full article
(This article belongs to the Special Issue Metabolic Engineering of Plants)
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46 pages, 3825 KiB  
Review
Lipid Mediators Regulate Pulmonary Fibrosis: Potential Mechanisms and Signaling Pathways
by Vidyani Suryadevara, Ramaswamy Ramchandran, David W. Kamp and Viswanathan Natarajan
Int. J. Mol. Sci. 2020, 21(12), 4257; https://doi.org/10.3390/ijms21124257 - 15 Jun 2020
Cited by 101 | Viewed by 13240
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown etiology characterized by distorted distal lung architecture, inflammation, and fibrosis. The molecular mechanisms involved in the pathophysiology of IPF are incompletely defined. Several lung cell types including alveolar epithelial cells, fibroblasts, monocyte-derived [...] Read more.
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown etiology characterized by distorted distal lung architecture, inflammation, and fibrosis. The molecular mechanisms involved in the pathophysiology of IPF are incompletely defined. Several lung cell types including alveolar epithelial cells, fibroblasts, monocyte-derived macrophages, and endothelial cells have been implicated in the development and progression of fibrosis. Regardless of the cell types involved, changes in gene expression, disrupted glycolysis, and mitochondrial oxidation, dysregulated protein folding, and altered phospholipid and sphingolipid metabolism result in activation of myofibroblast, deposition of extracellular matrix proteins, remodeling of lung architecture and fibrosis. Lipid mediators derived from phospholipids, sphingolipids, and polyunsaturated fatty acids play an important role in the pathogenesis of pulmonary fibrosis and have been described to exhibit pro- and anti-fibrotic effects in IPF and in preclinical animal models of lung fibrosis. This review describes the current understanding of the role and signaling pathways of prostanoids, lysophospholipids, and sphingolipids and their metabolizing enzymes in the development of lung fibrosis. Further, several of the lipid mediators and enzymes involved in their metabolism are therapeutic targets for drug development to treat IPF. Full article
(This article belongs to the Special Issue Emerging Role of Lipids in Metabolism and Disease)
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14 pages, 2204 KiB  
Article
A Novel Lysophosphatidic Acid Acyltransferase of Escherichia coli Produces Membrane Phospholipids with a cis-vaccenoyl Group and Is Related to Flagellar Formation
by Yosuke Toyotake, Masayoshi Nishiyama, Fumiaki Yokoyama, Takuya Ogawa, Jun Kawamoto and Tatsuo Kurihara
Biomolecules 2020, 10(5), 745; https://doi.org/10.3390/biom10050745 - 11 May 2020
Cited by 7 | Viewed by 3821
Abstract
Lysophosphatidic acid acyltransferase (LPAAT) introduces fatty acyl groups into the sn-2 position of membrane phospholipids (PLs). Various bacteria produce multiple LPAATs, whereas it is believed that Escherichia coli produces only one essential LPAAT homolog, PlsC—the deletion of which is lethal. However, we [...] Read more.
Lysophosphatidic acid acyltransferase (LPAAT) introduces fatty acyl groups into the sn-2 position of membrane phospholipids (PLs). Various bacteria produce multiple LPAATs, whereas it is believed that Escherichia coli produces only one essential LPAAT homolog, PlsC—the deletion of which is lethal. However, we found that E. coli possesses another LPAAT homolog named YihG. Here, we show that overexpression of YihG in E. coli carrying a temperature-sensitive mutation in plsC allowed its growth at non-permissive temperatures. Analysis of the fatty acyl composition of PLs from the yihG-deletion mutant (∆yihG) revealed that endogenous YihG introduces the cis-vaccenoyl group into the sn-2 position of PLs. Loss of YihG did not affect cell growth or morphology, but ∆yihG cells swam well in liquid medium in contrast to wild-type cells. Immunoblot analysis showed that FliC was highly expressed in ∆yihG cells, and this phenotype was suppressed by expression of recombinant YihG in ∆yihG cells. Transmission electron microscopy confirmed that the flagellar structure was observed only in ∆yihG cells. These results suggest that YihG has specific functions related to flagellar formation through modulation of the fatty acyl composition of membrane PLs. Full article
(This article belongs to the Special Issue Perspectives on Bacterial Flagellar Motor)
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