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Keywords = desaturase enzymes

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15 pages, 6331 KiB  
Article
Integrative Analysis of Iso-Seq and RNA-Seq Identifies Key Genes Related to Fatty Acid Biosynthesis and High-Altitude Stress Adaptation in Paeonia delavayi
by Qiongji He, Wenjue Yuan, Rui Wang, Wengao Yang, Guiqing He, Jinglong Cao, Yan Li, Lei Ye, Zhaoguang Li and Zhijiang Hou
Genes 2025, 16(8), 919; https://doi.org/10.3390/genes16080919 - 30 Jul 2025
Viewed by 190
Abstract
Background/Objectives: Paeonia delavayi, a high-altitude-adapted medicinal and oil-producing plant, exhibits broad elevational distribution. Understanding how environmental factors regulate its growth across altitudes is critical for optimizing cultivation and exploiting its economic potential. Methods: In this study, we conducted a comprehensive Iso-Seq [...] Read more.
Background/Objectives: Paeonia delavayi, a high-altitude-adapted medicinal and oil-producing plant, exhibits broad elevational distribution. Understanding how environmental factors regulate its growth across altitudes is critical for optimizing cultivation and exploiting its economic potential. Methods: In this study, we conducted a comprehensive Iso-Seq and RNA-seq analysis to elucidate the transcriptional profile across diverse altitudes and three seed developmental stages. Results: Using Pacbio full-length cDNA sequencing, we identified 39,267 full-length transcripts, with 80.03% (31,426) achieving successful annotation. RNA-seq analysis uncovered 11,423 and 9565 differentially expressed genes (DEGs) in response to different altitude and developmental stages, respectively. KEGG analysis indicated that pathways linked to fatty acid metabolism were notably enriched during developmental stages. In contrast, pathways associated with amino acid and protein metabolism were significantly enriched under different altitudes. Furthermore, we identified 34 DEGs related to fatty acid biosynthesis, including genes encoding pivotal enzymes like biotin carboxylase, carboxyl transferase subunit alpha, malonyl-CoA-acyl carrier protein transacylase, 3-oxoacyl-ACP reductase, 3-hydroxyacyl-ACP dehydratase, and stearoyl-ACP desaturase enoyl-ACP reductase. Additionally, ten DEGs were pinpointed as potentially involved in high-altitude stress response. Conclusions: These findings provide insights into the molecular mechanisms of fatty acid biosynthesis and adaptation to high-altitude stress in peony seeds, providing a theoretical foundation for future breeding programs aimed at enhancing seed quality. Full article
(This article belongs to the Section Genes & Environments)
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14 pages, 1607 KiB  
Article
Characterization and Expression Analysis of the Sterol C-5 Desaturase Gene PcERG3 in the Mycobiont of the Lichen Peltigera canina Under Abiotic Stresses
by Moatasem A. Swid, Milana V. Koulintchenko, Alfred O. Onele, Ilya Y. Leksin, Daniya F. Rakhmatullina, Ekaterina I. Galeeva, Julia N. Valitova, Farida V. Minibayeva and Richard P. Beckett
Microbiol. Res. 2025, 16(7), 139; https://doi.org/10.3390/microbiolres16070139 - 1 Jul 2025
Viewed by 295
Abstract
Lichens, symbiotic organisms with a high tolerance to harsh environments, possess a greater diversity of sterols than other organisms. Sterols are involved in maintaining membrane integrity, hormone biosynthesis, and signal transduction. (1) Background: A characteristic feature of lichen sterols is a high degree [...] Read more.
Lichens, symbiotic organisms with a high tolerance to harsh environments, possess a greater diversity of sterols than other organisms. Sterols are involved in maintaining membrane integrity, hormone biosynthesis, and signal transduction. (1) Background: A characteristic feature of lichen sterols is a high degree of unsaturation, which influences membrane properties. Desaturases play an important role in the synthesis of unsaturated sterols, in particular, sterol C-5 desaturase (ERG3), which controls the conversion of episterol to ergosterol. Earlier, we demonstrated that the treatment of the lichen Peltigera canina with low and elevated temperatures results in changes in the levels of episterol and ergosterol. (2) Methods: Here, for the first time, we identified ERG3 in P. canina and, using an in silico analysis, we showed that PcERG3 belongs to the superfamily of fatty acid hydrolyases. A phylogenetic analysis was conducted to determine the evolutionary relationships of PcERG3. (3) Results: A phylogenetic analysis showed that PcERG3 clusters with ERG3 from other Peltigeralian and non-Peltigeralian lichens and also with ERG3 from free-living fungi. This suggests that PcERG3 has an ancient evolutionary origin and is related to fungi with lichenized ancestors, e.g., Penicillium. The differential expression of PcERG3 in response to temperature stress, a dehydration/rehydration cycle, and heavy metal exposure suggests that it plays a crucial role in maintaining the balance between more and less saturated sterols and, more generally, in membrane functioning. The multifaceted response of P. canina to abiotic stresses was documented by simultaneously measuring changes in the expression of PcERG3, as well as the genes encoding the heat shock proteins, PcHSP20 and PcHSP98, and PcSOD1, which encodes the antioxidant enzyme superoxide dismutase. (4) Conclusions: These findings suggest that PcERG3 is similar to the sterol C-5 desaturases from related and free-living fungi and plays important roles in the molecular mechanisms underlying the tolerance of lichens to environmental stress. Full article
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12 pages, 481 KiB  
Article
Association Between Low Omega-6 Polyunsaturated Fatty Acid Levels and the Development of Delirium in the Coronary Intensive Care Unit
by Yurina Sugita-Yamaguchi, Tetsuro Miyazaki, Kazunori Shimada, Megumi Shimizu, Shohei Ouchi, Tatsuro Aikawa, Tomoyuki Shiozawa, Kiyoshi Takasu, Masaru Hiki, Shuhei Takahashi, Katsuhiko Sumiyoshi and Tohru Minamino
Nutrients 2025, 17(12), 1979; https://doi.org/10.3390/nu17121979 - 11 Jun 2025
Viewed by 513
Abstract
Background: Delirium is frequently observed in patients admitted to the intensive care unit, and is associated with mortality and morbidity. Although several studies have reported an association between polyunsaturated fatty acids (PUFAs) and cognitive disorders, the association between PUFA levels and development of [...] Read more.
Background: Delirium is frequently observed in patients admitted to the intensive care unit, and is associated with mortality and morbidity. Although several studies have reported an association between polyunsaturated fatty acids (PUFAs) and cognitive disorders, the association between PUFA levels and development of delirium in patients with acute cardiovascular disease remains unknown. Objective: This study aimed to clarify the association between PUFA levels and development of delirium in the coronary intensive care unit (CICU). Methods: We enrolled 590 consecutive patients (mean age, 70 ± 14 years) admitted to the CICU of Juntendo University Hospital. Fasting serum PUFA levels were measured within 24 h of admission. Delta-5 desaturase activity was estimated as the ratio of arachidonic acid (AA) to dihomo-gamma-linolenic acid (DGLA). Furthermore, delirium was defined as patients having a delirium score of ≥4 using the Intensive Care Delirium Screening Checklist. Results: Delirium was observed in 55 patients. DGLA levels were significantly lower, and delta-5 desaturase activity was significantly higher in patients with delirium than in those without delirium (both p < 0.001). Conversely, AA alone and omega-3 PUFAs did not differ between the groups. Additionally, DGLA and AA levels, but not omega-3 PUFA levels, were negatively associated; delta-5 desaturase activity was positively associated with the delirium score (both p < 0.001). The duration of delirium was significantly associated with DGLA and AA levels (p = 0.001 and p = 0.004, respectively). Moreover, multivariate analysis showed that decreased DGLA and increased delta-5 desaturase activity remained significant predictors of delirium. Conclusions: Low omega-6 PUFA levels and high delta-5 desaturase activity on admission were significantly associated with the development of delirium in the CICU, indicating that the evaluation of low omega-6 PUFA levels and related enzymes may identify patients at a high risk of developing delirium. Full article
(This article belongs to the Section Clinical Nutrition)
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21 pages, 2184 KiB  
Article
Dissecting the Molecular Mechanism of 10-HDA Biosynthesis: Role of Acyl-CoA Delta(11) Desaturase and Transcriptional Regulators in Honeybee Mandibular Glands
by Yunchang Li, Xiaojing Zhang, Zhenyu Xia and Yue Hao
Insects 2025, 16(6), 563; https://doi.org/10.3390/insects16060563 - 26 May 2025
Viewed by 768
Abstract
10-Hydroxy-2-decenoic acid (10-HDA), a major fatty acid (FA) component of royal jelly, is synthesized in the mandibular glands (MGs) of worker honeybees. Despite its well-documented nutritional and therapeutic significance, the biosynthetic pathway and regulatory mechanisms of 10-HDA production remain largely unresolved. In this [...] Read more.
10-Hydroxy-2-decenoic acid (10-HDA), a major fatty acid (FA) component of royal jelly, is synthesized in the mandibular glands (MGs) of worker honeybees. Despite its well-documented nutritional and therapeutic significance, the biosynthetic pathway and regulatory mechanisms of 10-HDA production remain largely unresolved. In this study, the molecular basis of 10-HDA biosynthesis and regulation in the MGs of newly emerged bees (NEBs), nurse bees (NBs), and forager bees (FBs) were investigated using RNA sequencing and weighted gene co-expression network analysis (WGCNA). A five-step biosynthetic pathway for 10-HDA was proposed, and cross-species analysis of Apis mellifera and A. cerana revealed the conserved expression patterns of 15 key enzymes involved. Functional validation via RNA interference (RNAi) demonstrated that knockdown of acyl-CoA Delta(11) desaturase (d11ds, LOC551527), a key enzyme in FA desaturation, led to a 50% reduction in 10-HDA levels. Protein–protein interaction (PPI) network analysis further identified transcriptional regulators Kay and Drep-2 as potential modulators of 10-HDA metabolism. This study provides the first comprehensive mechanistic model of 10-HDA biosynthesis in honeybee MGs and highlights the labor-specific regulation of FA metabolism. These findings offer promising genetic targets for improving the royal jelly quality through genetic technology. Full article
(This article belongs to the Special Issue Recent Studies on Resource Insects)
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23 pages, 1087 KiB  
Review
Nutrigenetics and Omega-3 and Gamma-Linolenic Acid Intake and Status in Patients with Cancer: A PRISMA Scoping Review of Research Trends and Challenges
by Vladica Zikic, Marija Paunovic, Marijana Milovic-Kovacevic, Vesna Vucic and Danijela Ristic-Medic
Int. J. Mol. Sci. 2025, 26(10), 4867; https://doi.org/10.3390/ijms26104867 - 19 May 2025
Viewed by 787
Abstract
Epidemiological studies report inconsistent findings regarding the association between dietary polyunsaturated fatty acid (PUFA) intake and cancer risk. Genetic variations—particularly single-nucleotide polymorphisms (SNPs) in the FADS1 and FADS2 genes—affect PUFA metabolism, linking circulating PUFA levels to the risk of several cancers, including breast, [...] Read more.
Epidemiological studies report inconsistent findings regarding the association between dietary polyunsaturated fatty acid (PUFA) intake and cancer risk. Genetic variations—particularly single-nucleotide polymorphisms (SNPs) in the FADS1 and FADS2 genes—affect PUFA metabolism, linking circulating PUFA levels to the risk of several cancers, including breast, colorectal, prostate, and pancreatic cancers. This review aimed to investigate the relationship between FADS1 and FADS2 gene variants and dietary intake, supplementation, or intervention with omega-3 fatty acids, gamma-linolenic acid (GLA), or their combination in cancer patients. A secondary objective was to examine genetically determined fatty acid profiles—shaped by FADS1 and FADS2 polymorphisms—in cancer patients without intervention and their potential association with PUFA-related cancer risk. A systematic search of the Scopus, PubMed, and Web of Science databases (up to 2024) identified 11 eligible studies out of 298 initial records. Analysis of the available literature suggests that specific FADS genotypes influence long-chain PUFA (LC-PUFA) concentrations in blood and tissues and that altered LC-PUFA levels may contribute to cancer development. The most consistent association identified is between the rs174537 variant and altered PUFA metabolism in prostate and breast cancer. However, conclusive evidence is lacking on the impact of dietary patterns on FADS desaturase activity or expression. Only one study has examined omega-3 supplementation in relation to FADS gene variants in prostate cancer patients, while the effects of GLA supplementation remain unexplored. Given the relative novelty of this research area and the limited number of studies, future investigations should integrate dietary PUFA intake, genetic variation in PUFA-metabolizing enzymes, and potential gene–nutrient interactions involving FADS gene polymorphisms and PUFAs to clarify their role in cancer risk. Full article
(This article belongs to the Special Issue Food Nutrition and Lipid Metabolism)
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16 pages, 1047 KiB  
Article
Effects and Mechanism of Nitrogen Regulation on Seed Yield and Quality of Rapeseed (Brassica napus L.)
by Chunli Wang, Xiaojun Wang, Jianli Yang, Zhi Zhang and Miaomiao Chen
Agronomy 2025, 15(5), 1232; https://doi.org/10.3390/agronomy15051232 - 19 May 2025
Viewed by 502
Abstract
Appropriate nitrogen is required and important in grain yield formation of crops. To elucidate nitrogen regulation of seed yield and quality of rapeseed (Brassica napus L.), field trials were consecutively conducted in two years with three nitrogen levels of 0, 180, and [...] Read more.
Appropriate nitrogen is required and important in grain yield formation of crops. To elucidate nitrogen regulation of seed yield and quality of rapeseed (Brassica napus L.), field trials were consecutively conducted in two years with three nitrogen levels of 0, 180, and 240 kg ha−1 (the N0, N180, and N240 treatments). The nitrogen application (N-app) induced increasing trend in the nitrogen accumulation in flowering plants (N-acc), number of siliques per plant (silique-num), number of branches per plant (branch-num), number of seeds per silique (seed-num), and seed yield of rapeseed; there were significant correlational relationships between these indexes (excepting seed-num). The N-app, N-acc, and silique-number showed higher effects on the seed yield. The effect of N-app was mainly achieved through influence on the silique-num, branch-num, and seed-num. When the N-app was increased from 180 to 240 kg ha−1, the nitrogen utilization efficiency (NUE) and the partial productivity of nitrogen fertilizer (PPN) of the rapeseed varieties tested showed a decreasing trend; the NR (nitrate reductase) gene expression level and the NR and GS (glutamine synthetase) activity in leaves was significantly increased under the N180 and N240 treatments compared to the N0 treatment, which achieved peak values at 180 kg ha−1 of N-app. The N-app hardly influenced the seed quality, as well as the gene expression and activity of the enzymes ACCase (acetyl-CoA carboxylase), FAD2 (oleic acid desaturase), and FAD3 (omega-3 fatty acid desaturase) in young seed. In conclusion, N-app induced significant increase in seed yield of rapeseed, the NR gene expression level and the NR and GS activity in leaves was improved; the NUE of rapeseed variety showed decreasing trend with increase in N-app level; while N-app hardly influenced the seed quality. Full article
(This article belongs to the Section Soil and Plant Nutrition)
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28 pages, 4689 KiB  
Article
Influence of Fatty Acid Desaturase Enzyme-1 Gene (FADS-1) Polymorphism on Serum Polyunsaturated Fatty Acids Levels, Desaturase Enzymes, Lipid Profile, and Glycemic Control Parameters in Newly Diagnosed Diabetic Mellitus Patients
by Hayder Huwais Jarullah and Eman Saadi Saleh
Int. J. Mol. Sci. 2025, 26(9), 4015; https://doi.org/10.3390/ijms26094015 - 24 Apr 2025
Viewed by 1557
Abstract
Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder caused by impaired insulin secretion from pancreatic β-cells and insulin resistance in target tissues. Genome-wide association studies have identified over 50 genetic variants linked to T2DM, including polymorphisms associated with the disease. This [...] Read more.
Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder caused by impaired insulin secretion from pancreatic β-cells and insulin resistance in target tissues. Genome-wide association studies have identified over 50 genetic variants linked to T2DM, including polymorphisms associated with the disease. This study investigates the impact of the FADS1 (rs174547) polymorphism in T2DM patients compared to healthy controls and examines serum levels of omega-3 and omega-6 fatty acids, as well as D5D and D6D enzyme levels and activity. This case–control study included 120 participants: 60 newly diagnosed T2DM patients and 60 apparently healthy controls matched for age, sex, and other sociodemographic factors. Polyunsaturated fatty acid (PUFA) levels and desaturase enzyme activities in the n-3 and n-6 pathways were assessed using ELISA and gas chromatography. FADS1 gene polymorphisms were analyzed via Sanger sequencing. Genotype and allele frequencies of FADS1 (rs174547) differed significantly between groups, with higher frequencies of C-containing alleles in T2DM patients. Multivariate analysis revealed a significant association between the C-allele genotype and increased T2DM risk, independent of sociodemographic variables, lipid profile, and inflammatory markers. In conclusion; reduced serum levels of omega-3 and omega-6 fatty acids in T2DM were associated with decreased desaturase enzyme activity. The FADS1 (rs174547) polymorphism is significantly associated with T2DM risk, with the minor allele linked to lower desaturase activity. Full article
(This article belongs to the Special Issue Advances in Molecular Research of Diabetes Mellitus)
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29 pages, 4883 KiB  
Article
High-Fat Diet in Perinatal Period Promotes Liver Steatosis and Low Desaturation Capacity of Polyunsaturated Fatty Acids in Dams: A Link with Anxiety-Like Behavior in Rats
by Lorena Mercado-López, Yasna Muñoz, Camila Farias, María Paz Beyer, Robinson Carrasco-Gutiérrez, Angie Vanessa Caicedo-Paz, Alexies Dagnino-Subiabre, Alejandra Espinosa and Rodrigo Valenzuela
Nutrients 2025, 17(7), 1180; https://doi.org/10.3390/nu17071180 - 28 Mar 2025
Viewed by 869
Abstract
Background/Objectives: This study investigates the effects of a high-fat diet (HFD) during pregnancy and lactation on maternal and offspring health, focusing on behavioral, metabolic, and fatty acid composition outcomes in a rat model. Methods: Twelve female Sprague–Dawley rats were fed either a control [...] Read more.
Background/Objectives: This study investigates the effects of a high-fat diet (HFD) during pregnancy and lactation on maternal and offspring health, focusing on behavioral, metabolic, and fatty acid composition outcomes in a rat model. Methods: Twelve female Sprague–Dawley rats were fed either a control diet, CD (n = 6), or HFD (n = 6) for 12 weeks, encompassing mating, gestation, and lactation periods (18 weeks). Anxiety-like behavior, maternal behavior, depression-like behavior, and social play were studied. Post mortem, the liver function, hepatic steatosis, and fatty acid composition (erythrocytes, liver, adipose tissue) were evaluated. In regard to desaturase enzymes (Δ-6D and Δ-5D), liver activity, protein mass, and gene expression (RT-PCR) were analyzed. Additionally, gene expression of PPAR-α, ACOX, CPT1-α, SREBP-1c, ACC, and FAS was assessed. Statistical analysis was performed using Student’s t-test, mean ± SD (p < 0.05). Results: The HFD significantly increased maternal weight and anxiety-like behavior while reducing social interactions exclusively in male offspring (p < 0.05). It also led to a significant decrease in the synthesis and content of n-3 PUFAs in the analyzed tissues, induced hepatic steatosis, and upregulated the expression of pro-lipogenic genes in the maternal liver. Conclusions: These findings suggest that long-term HFD consumption alters tissue fatty acid composition, disrupts metabolic homeostasis, and contributes to behavioral changes, increasing anxiety-like behaviors in pregnant dams and reducing social interactions in male offspring. Overall, this study provides further insight into the detrimental effects of HFD consumption during the perinatal period. Full article
(This article belongs to the Special Issue Dietary Fatty Acids and Metabolic Health)
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16 pages, 3165 KiB  
Article
The Positive Effect of Akkermansia muciniphila postbiotics on the Glycolipid Metabolism of Caenorhabditis elegans Induced by High-Glucose Diet
by Zhongqin Wu, Ke Li, Aixing Hou, Yuanliang Wang and Zongjun Li
Nutrients 2025, 17(6), 976; https://doi.org/10.3390/nu17060976 - 11 Mar 2025
Viewed by 1275
Abstract
Background: Glycolipid metabolism is essential for maintaining metabolic homeostasis. As a new postbiotic, pasteurized Akkermansia muciniphila (P-AKK) is important for the regulation of immunity and metabolism. Objectives: This study aimed to evaluate the effects of P-AKK on glycolipid metabolism in Caenorhabditis elegans fed [...] Read more.
Background: Glycolipid metabolism is essential for maintaining metabolic homeostasis. As a new postbiotic, pasteurized Akkermansia muciniphila (P-AKK) is important for the regulation of immunity and metabolism. Objectives: This study aimed to evaluate the effects of P-AKK on glycolipid metabolism in Caenorhabditis elegans fed a high glucose diet. Results: We discovered that feeding nematodes P-AKK improved their healthy lifespan when fed a high-glucose diet. Furthermore, P-AKK contributes to reducing the accumulation of glucose, advanced glycation end products, and lipids and maintains a better physiological state. In addition, P-AKK improved the composition of free fatty acids and decreased the total free fatty acid content of C. elegans. Transcriptome sequencing analysis revealed that P-AKK induced significant enrichment of carbohydrate, oxidative phosphorylation, and fatty acid metabolism pathways. These significantly enriched biological processes were closely related to glucose and lipid metabolism. Among them, P-AKK activated the β-oxidation of fatty acids while inhibiting the de novo synthesis of fatty acids to regulate fatty acid metabolism. Conclusions: The administration of P-AKK positively affected the body phenotypes of C. elegans under high glucose conditions. P-AKK mitigated the fat accumulation induced by a high-glucose diet by regulating key metabolic enzymes, including acyl-CoA synthetase and stearoyl-CoA desaturase. Full article
(This article belongs to the Special Issue Effects of Probiotics, Prebiotics, and Postbiotics on Human Health)
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14 pages, 4382 KiB  
Article
Dietary Methionine Hydroxy Analog Regulates Hepatic Lipid Metabolism via SIRT1/AMPK Signaling Pathways in Largemouth Bass Micropterus salmodies
by Ju Zhao, Zhongjie Yang, Haifeng Liu, Chao Yang, Yujun Chen, Quanquan Cao and Jun Jiang
Biology 2025, 14(3), 227; https://doi.org/10.3390/biology14030227 - 21 Feb 2025
Viewed by 797
Abstract
This experiment was arranged to explore the impacts of dietary MHA on liver lipid metabolism in largemouth bass. A total of 480 fish (14.49 ± 0.13 g) were randomly allocated into four groups, each with three replicates. They were then given four different [...] Read more.
This experiment was arranged to explore the impacts of dietary MHA on liver lipid metabolism in largemouth bass. A total of 480 fish (14.49 ± 0.13 g) were randomly allocated into four groups, each with three replicates. They were then given four different diets containing graded levels of MHA (0.0, 3.0, 6.0, and 9.0 g/kg) for 84 days. The results showed that dietary MHA increased hepatic lipid vacuoles and lipid content (p < 0.05). Dietary supplementation with MHA 9.0 g/kg diets increased the activities of acetyl-coA carboxylase (ACC), fatty acid synthase (FAS), and stearoyl-coA desaturase 1 (SCD-1). Dietary MHA up-regulated the mRNA expressions of liver lipid synthesis (ACC, FAS, SCD-1 and SREBP-1c) (p < 0.05). Furthermore, compared with the 0.0 g/kg diet group, the group supplemented with 9.0 g/kg MHA in the diet exhibited a significant decrease in the activities of liver lipid-oxidation-related enzymes (acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and stearoyl-CoA desaturase 1 (SCD-1), as well as HSL and CPT1) and the gene expressions of ATGL, HSLa, HSLb, CPT1a, and PPARα (p < 0.05). Additionally, the mRNA expressions and protein levels of SIRT1 and AMPK in the 9.0 g/kg MHA-supplemented group were significantly lower than those in the 0.0 g/kg diet group (p < 0.05). Overall, the present results suggested that dietary MHA could increase lipid accumulation through regulating SIRT1/AMPK signaling pathways in the livers of largemouth bass. Full article
(This article belongs to the Special Issue Nutrition, Environment, and Fish Physiology)
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13 pages, 1313 KiB  
Article
Product Speculation from Carotenogenic Gene Cluster of Nonlabens spongiae Genome, and Identification of Myxol and Functional Analysis of Each Gene
by Keisuke Nakazawa, Daiki Mineo, Takuya Harayama, Susumu Yoshizawa, Shinichi Takaichi and Kenjiro Sugiyama
Genes 2025, 16(2), 202; https://doi.org/10.3390/genes16020202 - 7 Feb 2025
Cited by 1 | Viewed by 1025
Abstract
Background: Myxol, a monocyclic carotenoid with β- and ψ-end groups, has been identified in only a limited number of bacteria, such as flavobacteria and cyanobacteria. Despite its biological significance, the biosynthetic pathway of myxol is not well understood, and studies on its physiological [...] Read more.
Background: Myxol, a monocyclic carotenoid with β- and ψ-end groups, has been identified in only a limited number of bacteria, such as flavobacteria and cyanobacteria. Despite its biological significance, the biosynthetic pathway of myxol is not well understood, and studies on its physiological functions and biological activities are limited because of its rarity. Methods: BLAST homology searches for carotenoid biosynthesis genes in the genome of Nonlabens were performed. The carotenogenesis-related genes in the genome of the marine flavobacteria Nonlabens spongiae were individually cloned and functionally characterized using a heterologous Escherichia coli expression system. Carotenoids from N. spongiae were identified using an LC-MS analysis. Results: We identified a gene cluster involved in carotenoid biosynthesis in the genome of N. spongiae. This cluster includes genes encoding phytoene synthase (CrtB), phytoene desaturase (CrtI), lycopene cyclase (CrtY), carotenoid 1,2-hydratase (CruF), carotenoid 3,4-desaturase (ψ-end group) (CrtD), carotenoid 2-hydroxylase (ψ-end group) (CrtA-OH), and carotene hydro-xylase (CrtZ). Based on the characteristics of these enzymes, the primary products were predicted to be myxol and/or zeaxanthin. A spectroscopic analysis confirmed that myxol was the primary carotenoid. Furthermore, a plasmid containing a reconstructed gene cluster and geranylgeranyl pyrophosphate synthase (CrtE) located outside the cluster was introduced into E. coli. This system predominantly accumulated myxol, indicating that the reconstructed gene cluster enabled efficient myxol production in E. coli. Conclusions: This study highlighted the potential biotechnological applications of the carotenoid biosynthesis gene clusters for myxol production. Full article
(This article belongs to the Section Microbial Genetics and Genomics)
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14 pages, 4090 KiB  
Article
Lipids Metabolism Inhibition Antiproliferative Synergy with 5-Fluorouracil in Human Colorectal Cancer Model
by Judyta Zabielska, Ewa Stelmanska, Sylwia Szrok-Jurga, Jarosław Kobiela and Aleksandra Czumaj
Int. J. Mol. Sci. 2025, 26(3), 1186; https://doi.org/10.3390/ijms26031186 - 30 Jan 2025
Cited by 3 | Viewed by 1144
Abstract
Colorectal cancer (CRC) is recognized as the third most lethal cancer worldwide. While existing treatment options demonstrate considerable efficacy, they are often constrained by non-selectivity and substantial side effects. Recent studies indicate that lipid metabolism significantly influences carcinogenesis, highlighting it as a promising [...] Read more.
Colorectal cancer (CRC) is recognized as the third most lethal cancer worldwide. While existing treatment options demonstrate considerable efficacy, they are often constrained by non-selectivity and substantial side effects. Recent studies indicate that lipid metabolism significantly influences carcinogenesis, highlighting it as a promising avenue for developing targeted anticancer therapies. The purpose of the study was to see if acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), and stearoyl-CoA 9-desaturase (SCD1) are good metabolic targets and whether the use of inhibitors of these enzymes together with 5-fluorouracil (5-FU) would have a synergistic effect on CRC cell viability. To confirm that the correct lipid targets were chosen, the expression levels of ACAT1, HMGCR, and SCD1 were examined in CRC patients and cell models. At first, each compound (Avasimibe, Lovastatin, MF-438, and 5-FU was tested separately, and then each inhibitor was paired with 5-FU to assess the synergistic effect on cell viability. Gene expression of selected enzymes significantly increased in tissue samples obtained from CRC patients and cancer cell lines (HT-29). Inhibition of any of the selected enzymes reduced CRC cell growth in a dose-dependent manner. More importantly, the combination of 5-FU + Avasimibe (an ACAT1 inhibitor) and 5-FU + MF-438 (an SCD1 inhibitor) produced a stronger antiproliferative effect than the inhibitors alone. 5-FU combined either with Avasimibe or MF-438 showed a synergistic effect with an HSA score of 47.00 at a dose of 0.3 + 30 µM, respectively (2.66% viability rate vs. 46%; p < 0.001), and 39.34 at a dose of 0.3 + 0.06 µM (46% vs. 10.33%; p < 0.001), respectively. The association of 5-FU with Lovastatin (HMGCR inhibitor) did not significantly impact CRC cell viability in a synergistic manner. Inhibition of lipid metabolism combined with standard chemotherapy is a promising strategy that reduces CRC cell viability and allows for the use of a lower drug dose. The combination of 5-FU and Avasimibe has the greatest therapeutic potential among studied compounds. Full article
(This article belongs to the Special Issue CoA in Health and Disease 3.0)
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14 pages, 2393 KiB  
Article
Salicylic Acid Improved the Growth of Dunaliella salina and Increased the Proportion of 9-cis-β-Carotene Isomers
by Shuaicheng Xiang, Xiaoting Qiu, Xiaojun Yan, Roger Ruan and Pengfei Cheng
Mar. Drugs 2025, 23(1), 18; https://doi.org/10.3390/md23010018 - 1 Jan 2025
Cited by 1 | Viewed by 2000
Abstract
Dunaliella salina is an important source of natural β-carotene (containing 9-cis and all trans isomers) for industrial production. The phytohormone salicylic acid (SA) has been proven to have impacts on the stress resistance of higher plants, but research on microalgae is currently unclear. [...] Read more.
Dunaliella salina is an important source of natural β-carotene (containing 9-cis and all trans isomers) for industrial production. The phytohormone salicylic acid (SA) has been proven to have impacts on the stress resistance of higher plants, but research on microalgae is currently unclear. In this study, the effects of SA on the growth, biochemical composition, antioxidant enzyme activity, key enzymes of β-carotene synthesis, and cis-and trans-isomers of β-carotene in D. salina under different salt concentrations were investigated. The results were shown that at concentrations of 1.5, 2, and 2.5 M NaCl, the antioxidant enzyme activity and key enzymes for β-carotene synthesis in algal cells were significantly increased, but the content and proportion of 9-cis isomer in β-carotene isomers decreased. The addition of SA significantly increased the growth and antioxidant enzyme (SOD, MDA) activity, as well as the synthesis of key enzyme phytoene synthase (PSY), phytoene desaturase (PDS), and lycopene β cyclase (LCYB) of D. salina under high-salinity conditions. It is worth noting that under the treatment of SA, the proportion of 9-cis isomer in the three salt concentrations (1.5, 2, 2.5 M NaCl) significantly increased by 32.09%, 20.30%, and 11.32%, respectively. Moreover, SA can not only improve the salt tolerance of D. salina, but also increase the proportion of 9-cis isomer, with higher physiological activity in β-carotene, thereby enhancing the application value of D. salina. Full article
(This article belongs to the Special Issue Biotechnological Applications of Marine Photosynthetic Microorganisms)
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17 pages, 9066 KiB  
Article
Genetic Variants Affecting FADS2 Enzyme Dynamics and Gene Expression in Cogenetic Oysters with Different PUFA Levels Provide New Tools to Improve Unsaturated Fatty Acids
by Qingyuan Li, Chaogang Wang, Ao Li, Haigang Qi, Wei Wang, Xinxing Wang, Guofan Zhang and Li Li
Int. J. Mol. Sci. 2024, 25(24), 13551; https://doi.org/10.3390/ijms252413551 - 18 Dec 2024
Viewed by 1200
Abstract
Long-chain polyunsaturated fatty acids (LC-PUFAs) are crucial for human health and cannot be produced internally. Bivalves, such as oysters, serve as valuable sources of high-quality PUFAs. The enzyme fatty acid desaturase (FADS) plays a key role in the metabolism of LC-PUFAs. In this [...] Read more.
Long-chain polyunsaturated fatty acids (LC-PUFAs) are crucial for human health and cannot be produced internally. Bivalves, such as oysters, serve as valuable sources of high-quality PUFAs. The enzyme fatty acid desaturase (FADS) plays a key role in the metabolism of LC-PUFAs. In this study, we conducted a thorough genome-wide analysis of the genes belong to the FADS family in Crassostrea gigas and Crassostrea angulata, with the objective of elucidating the function of the FADS2 and investigating the genetic variations that affect PUFA biosynthesis. We identified six FADS genes distributed across four chromosomes, categorized into three subfamilies. The coding region of FADS2 revealed five non-synonymous mutations that were shown to influence protein structure and stability through molecular dynamics simulations. The promoter region of FADS2 contains ten SNPs and three indels significantly correlated with PUFA content. These genetic variations may explain the differences in PUFA levels observed between the two oyster species and could have potential applications in enhancing PUFA content. This study improves the molecular understanding of PUFA metabolism in oysters and presents a potential strategy for selecting oysters with high PUFA levels. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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14 pages, 3793 KiB  
Article
Effect of Ceramides Derivatives from the Peach on Skin Function Improvement in UV-Irradiated Hairless Mice
by Jinhee Kim, Minhee Lee, Wonhee Cho, Eunhee Yoo, Jinhak Kim, Yuri Gwon, Musashi Okayasu and Jeongmin Lee
Foods 2024, 13(23), 3824; https://doi.org/10.3390/foods13233824 - 27 Nov 2024
Viewed by 1611
Abstract
This study investigated the protective effects of a ceramides derivates from the peach (PF3) on photoaging by UV-irradiated hairless mice. Mice were randomly divided into seven groups: AIN93G without UVB exposure (normal control, NC), AIN93G with UVB exposure (control, C), AIN93G supplemented 100 [...] Read more.
This study investigated the protective effects of a ceramides derivates from the peach (PF3) on photoaging by UV-irradiated hairless mice. Mice were randomly divided into seven groups: AIN93G without UVB exposure (normal control, NC), AIN93G with UVB exposure (control, C), AIN93G supplemented 100 mg/kg body weight (BW) of L-ascorbic acid with UVB exposure (AA), AIN93G supplemented 100 mg/kg BW of arbutin with UVB exposure (Arbutin), AIN93G supplemented 10 mg/kg BW of PF3 with UVB exposure (10PF3), AIN93G supplemented 20 mg/kg BW of PF3 with UVB exposure (20PF3), and AIN93G supplemented 40 mg/kg BW of PF3 with UVB exposure (40PF3). The study examined the impact of PF3 on skin hydration, wrinkle formation, and melanogenesis using enzyme-linked immunosorbent assay (ELISA), real-time polymerase chain reaction (real-time PCR), and Western blot analysis. The PF3 demonstrated significant protective effects against photoaging by reducing skin wrinkle formation, decreasing epidermal and dermal thickening, and improving skin hydration. It also enhanced the expression of moisture-related factors (hyaluronic acid synthase [HAS], long-chain ceramides [LCBs], dihydroceramide desaturase 1 [DEGS1], and type I collagen [COL1A]) and antioxidant enzyme activities while reducing pro-inflammatory cytokines and oxidative stress markers. The PF3 supplementation positively modulated skin wrinkle formation-related factors, increasing collagen-related gene expression and decreasing matrix metalloproteinases. Additionally, PF3 showed potential in regulating melanogenesis by reducing the nitric oxide and cAMP content, as well as the expression of melanogenesis-related proteins. These comprehensive findings suggest that PF3 supplementation may be an effective strategy for preventing and treating UVB-induced skin photoaging through multiple mechanisms, including improved skin structure, hydration, antioxidant defense, and reduced inflammation and pigmentation. Full article
(This article belongs to the Section Food Nutrition)
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