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15 pages, 3023 KiB  
Article
Developmental and Molecular Effects of C-Type Natriuretic Peptide Supplementation in In Vitro Culture of Bovine Embryos
by Camila Bortoliero Costa, Nathália Covre da Silva, Amanda Nespolo Silva, Elisa Mariano Pioltine, Thaisy Tino Dellaqua, Amanda Fonseca Zangirolamo, Flávio Vieira Meirelles, Marcelo Marcondes Seneda and Marcelo Fábio Gouveia Nogueira
Int. J. Mol. Sci. 2024, 25(20), 10938; https://doi.org/10.3390/ijms252010938 - 11 Oct 2024
Viewed by 227
Abstract
The use of C-type natriuretic peptide (CNP) in the interaction with the oocyte and in the temporary postponement of spontaneous meiosis resumption has already been well described. However, its action in pre-implantation developmental-stage embryos is yet to be understood. Thus, our study aimed [...] Read more.
The use of C-type natriuretic peptide (CNP) in the interaction with the oocyte and in the temporary postponement of spontaneous meiosis resumption has already been well described. However, its action in pre-implantation developmental-stage embryos is yet to be understood. Thus, our study aimed to detect the presence of the canonical CNP receptor (natriuretic peptide receptor, NPR2) in germinal vesicle (GV)-, metaphase II (MII)-, presumptive zygote (PZ)-, morula (MO)-, and blastocyst (BL)-stage embryos and, later, to observe possible modulations on the embryos when co-cultured with CNP. In Experiment I, we detected and quantified NPR2 on the abovementioned embryo stages. Further, in Experiment II, we intended to test different concentrations (100, 200, or 400 nM of CNP) at different times of inclusion in the in vitro culture (IVC; inclusion from the beginning, i.e., day 1, or from day 5). In Experiment III, 400 nM of CNP was used on day 1 (D1) in the IVC, which was not demonstrated to be embryotoxic, and it showed potentially promising results in the blastocyst production rate when compared to the control. Thus, we analyzed the embryonic development rates of bovine embryos (D7) and hatching kinetics (D7, D8, and D9). Subsequently, morula and blastocyst were collected and evaluated for transcript abundance of their competence and quality (apoptosis, oxidative stress, proliferation, and differentiation) and lipid metabolism. Differences with probabilities less than p < 0.05, and/or fold change (FC) > 1.5, were considered significant. We demonstrate the presence of NPR2 until the blastocyst development stage, when there was a significant decrease in membrane receptors. There was no statistical difference in the production rate after co-culture with 400 nM CNP. However, when we evaluated the abundance of morula transcripts, there was an upregulated transcription in ADCY6 (p = 0.057) and downregulated transcripts in BMP15 (p = 0.013), ACAT1 (p = 0.040), and CASP3 (p = 0.082). In addition, there was a total of 12 transcriptions in morula that presented variation FC > 1.5. In blastocysts, the treatment with CNP induced upregulation in BID, CASP3, SOX2, and HSPA5 transcripts and downregulation in BDNF, NLRP5, ELOVL1, ELOVL4, IGFBP4, and FDX1 transcripts (FC > 1.5). Thus, our study identified and quantified the presence of NPR2 in bovine pre-implantation embryos. Furthermore, 400 nM of CNP in IVC, a concentration not previously described in the literature, modulated some transcripts related to embryonic metabolism, and this was not embryotoxic morphologically. Full article
(This article belongs to the Special Issue Molecular Research on Embryo Developmental Potential)
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17 pages, 514 KiB  
Article
Performance, Meat Quality and Gene Expression of Grazing Lambs Supplemented with Macadamia Oil and Vitamin E
by Paulo C. G. Dias Junior, Isabela J. dos Santos, Sarita B. Gallo, Tharcilla I. R. C. Alvarenga, Flavio A. P. Alvarenga, Adriana M. Garcia, Idalmo G. Pereira, Nadja G. Alves and Iraides F. Furusho-Garcia
Appl. Sci. 2024, 14(19), 8870; https://doi.org/10.3390/app14198870 - 2 Oct 2024
Viewed by 438
Abstract
Macadamia oil has high concentrations of oleic and palmitoleic fatty acids, which can increase tissue sensitivity to insulin, improving glucose absorption efficiency, and reducing lipogenesis through gene modulation. The objective of this study was to evaluate the effects of macadamia oil associated with [...] Read more.
Macadamia oil has high concentrations of oleic and palmitoleic fatty acids, which can increase tissue sensitivity to insulin, improving glucose absorption efficiency, and reducing lipogenesis through gene modulation. The objective of this study was to evaluate the effects of macadamia oil associated with vitamin E supplementation on performance, blood parameters, meat quality and sensory characteristics, meat fatty acid profile, and expression of genes associated with lipid metabolism in grazing lambs. The experimental treatments were control diet (Control), Control + 0.1% of body weight of macadamia oil (MO), MO + 745 IU of vitamin E/dry matter (MOVE). Macadamia oil improved feed efficiency, reflecting a lower dry matter intake, as the average daily weight gain did not differ from Control. Meat quality parameters were not affected by macadamia oil or vitamin E supplementation. Supplementation with macadamia oil improved meat appearance, flavor, and overall liking. Supplementation with macadamia oil provided a higher proportion of C18:3 n3 and a lower proportion of CLA. The expression of SREBP-1c, PPAR-α, SCD1, and ELOVL6 genes were not modified with the supplementation of macadamia oil and vitamin E. In conclusion, supplementation with macadamia oil improves feed efficiency and meat quality; and the inclusion of 745 IU of vitamin E/kg of dry matter for grazing lambs reduces 36% of lipid oxidation of the meat. Full article
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20 pages, 3373 KiB  
Article
Exploring the Role of MicroRNAs in Progesterone and Estrogen Receptor Expression in Endometriosis
by Jing-Xian Hon, Norhazlina Abdul Wahab, Abdul Kadir Abdul Karim, Norfilza Mohd Mokhtar and Mohd Helmy Mokhtar
Biomedicines 2024, 12(10), 2218; https://doi.org/10.3390/biomedicines12102218 - 28 Sep 2024
Viewed by 457
Abstract
Background/Objectives: Patients with endometriosis still respond poorly to progestins due to progesterone resistance associated with microRNAs (miRNAs). The aim of this study was to investigate the expression of selected miRNAs, estrogen receptor (ER)α, ERβ, progesterone receptor (PR)-A and PR-B and to determine [...] Read more.
Background/Objectives: Patients with endometriosis still respond poorly to progestins due to progesterone resistance associated with microRNAs (miRNAs). The aim of this study was to investigate the expression of selected miRNAs, estrogen receptor (ER)α, ERβ, progesterone receptor (PR)-A and PR-B and to determine the target genes of upregulated miRNAs in endometriosis. Methods: In this study, 18 controls, 18 eutopic and 18 ectopic samples were analysed. Profiling and validation of miRNAs associated with functions of endometriosis were performed using next-generation sequencing (NGS) and qRT-PCR. At the same time, the expression of ERα, ERβ, PR-A and PR-B was also determined using qRT-PCR. Target prediction was also performed for miR-199a-3p, miR-1-3p and miR-125b-5p using StarBase. Results: In this study, NGS identified seven significantly differentially expressed miRNAs, of which six miRNAs related to the role of endometriosis were selected for validation by qRT-PCR. The expression of miR-199a-3p, miR-1-3p, miR-146a-5p and miR-125b-5p was upregulated in the ectopic group compared to the eutopic group. Meanwhile, ERα and ERβ were significantly differentially expressed in endometriosis compared to the control group. However, the expressions of PR-A and PR-B showed no significant differences between the groups. The predicted target genes for miR-199a-3p, miR-1-3p and miR-125b-5p are SCD, TAOK1, DDIT4, LASP1, CDK6, TAGLN2, G6PD and ELOVL6. Conclusions: Our findings demonstrated that the expressions of ERα and ERβ might be regulated by miRNAs contributing to progesterone resistance, whereas the binding of miRNAs to target genes could also contribute to the pathogenesis of endometriosis. Therefore, miRNAs could be used as potential biomarkers and for targeted therapy in patients with endometriosis. Full article
(This article belongs to the Special Issue MicroRNA and Its Role in Human Health)
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18 pages, 8177 KiB  
Article
Combining Transcriptomics and Proteomics to Screen Candidate Genes Related to Bovine Birth Weight
by Xiuyuan Wang, Ruili Liu, Zhenpeng Chen, Renzheng Zhang, Yanfang Mei, Xiuping Miao, Xuejin Bai and Yajuan Dong
Animals 2024, 14(18), 2751; https://doi.org/10.3390/ani14182751 - 23 Sep 2024
Viewed by 499
Abstract
The placenta is a vital organ in bovine reproduction, crucial for blood supply, nutrient transport, and embryonic development. It plays an essential role in the intrauterine growth of calves. However, the molecular mechanisms governing placental function in calves remain inadequately understood. Methods: We [...] Read more.
The placenta is a vital organ in bovine reproduction, crucial for blood supply, nutrient transport, and embryonic development. It plays an essential role in the intrauterine growth of calves. However, the molecular mechanisms governing placental function in calves remain inadequately understood. Methods: We established transcriptome and proteome databases for low-birth-weight (LB) and high-birth-weight (HB) calf placentae, identifying key genes and proteins associated with birth weight through bioinformatics analyses that included functional enrichment and protein–protein interactions (PPIs). Both mRNA and protein levels were validated. Results: A total of 1494 differentially expressed genes (DEGs) and 294 differentially expressed proteins (DEPs) were identified when comparing the LB group to the HB group. Furthermore, we identified 53 genes and proteins exhibiting significant co-expression across both transcriptomic and proteomic datasets; among these, 40 were co-upregulated, 8 co-downregulated, while 5 displayed upregulation at the protein level despite downregulation at the mRNA level. Functional enrichment analyses (GO and KEGG) and protein–protein interaction (PPI) analysis indicate that, at the transcriptional level, the primary factor contributing to differences in calf birth weight is that the placenta of the high-birth-weight (HB) group provides more nutrients to the fetus, characterized by enhanced nutrient transport (SLC2A1 and SLC2A11), energy metabolism (ACSL1, MICALL2, PAG2, COL14A1, and ELOVL5), and lipid synthesis (ELOVL5 and ELOVL7). In contrast, the placenta of the low-birth-weight (LB) group prioritizes cell proliferation (PAK1 and ITGA3) and angiogenesis. At the protein level, while the placentae from the HB group exhibit efficient energy production and lipid synthesis, they also demonstrate reduced immunity to various diseases such as systemic lupus erythematosus and bacterial dysentery. Conversely, the LB group placentae excel in regulating critical biological processes, including cell migration, proliferation, differentiation, apoptosis, and signal transduction; they also display higher disease immunity markers (COL6A1, TNC CD36, CD81, Igh-1a, and IGHG) compared to those of the HB group placentae. Co-expression analysis further suggests that increases in calf birth weight can be attributed to both high-efficiency energy production and lipid synthesis within the HB group placentae (ELOVL5, ELOVL7, and ACSL1), alongside cholesterol biosynthesis and metabolic pathways involving CYP11A1 and CYP17A1. Conclusion: We propose that ELOVL5, ELOVL7, ACSL1, CYP11A1, and CYP17A1 serve as potential protein biomarkers for regulating calf birth weight through the modulation of the fatty acid metabolism, lipid synthesis, and cholesterol levels. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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13 pages, 3650 KiB  
Article
Sirtuin 1 Inhibits Fatty Acid Synthesis through Forkhead Box Protein O1-Mediated Adipose Triglyceride Lipase Expression in Goat Mammary Epithelial Cells
by Qiuya He, Weiwei Yao, Li Lv, Xuelin Zhang, Jiao Wu and Jun Luo
Int. J. Mol. Sci. 2024, 25(18), 9923; https://doi.org/10.3390/ijms25189923 - 14 Sep 2024
Viewed by 378
Abstract
Sirtuin 1 (SIRT1) is a key upstream regulator of lipid metabolism; however, the molecular mechanisms by which SIRT1 regulates milk fat synthesis in dairy goats remain unclear. This study aimed to investigate the regulatory roles of SIRT1 in modulating lipid metabolism in goat [...] Read more.
Sirtuin 1 (SIRT1) is a key upstream regulator of lipid metabolism; however, the molecular mechanisms by which SIRT1 regulates milk fat synthesis in dairy goats remain unclear. This study aimed to investigate the regulatory roles of SIRT1 in modulating lipid metabolism in goat mammary epithelial cells (GMECs) and its impact on the adipose triglyceride lipase (ATGL) promoter activity using RNA interference (RNAi) and gene overexpression techniques. The results showed that SIRT1 is significantly upregulated during lactation compared to the dry period. Additionally, SIRT1 knockdown notably increased the expressions of genes related to fatty acid synthesis (SREBP1, SCD1, FASN, ELOVL6), triacylglycerol (TAG) production (DGAT2, AGPAT6), and lipid droplet formation (PLIN2). Consistent with the transcriptional changes, SIRT1 knockdown significantly increased the intracellular contents of TAG and cholesterol and the lipid droplet abundance in the GMECs, while SIRT1 overexpression had the opposite effects. Furthermore, the co-overexpression of SIRT1 and Forkhead box protein O1 (FOXO1) led to a more pronounced increase in ATGL promoter activity, and the ability of SIRT1 to enhance ATGL promoter activity was nearly abolished when the FOXO1 binding sites (FKH1 and FKH2) were mutated, indicating that SIRT1 enhances the transcriptional activity of ATGL via the FKH element in the ATGL promoter. Collectively, our data reveal that SIRT1 enhances the transcriptional activity of ATGL through the FOXO1 binding sites located in the ATGL promoter, thereby regulating lipid metabolism. These findings provide novel insights into the role of SIRT1 in fatty acid metabolism in dairy goats. Full article
(This article belongs to the Special Issue Sirtuins as Players in Cell Metabolism and Functions)
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14 pages, 3173 KiB  
Article
MiR-206 Suppresses Triacylglycerol Accumulation via Fatty Acid Elongase 6 in Dairy Cow Mammary Epithelial Cells
by Xin Zhao, Yu Liu, Yupeng Li, Yuxin Zhang, Chunlei Yang and Dawei Yao
Animals 2024, 14(17), 2590; https://doi.org/10.3390/ani14172590 - 6 Sep 2024
Viewed by 380
Abstract
Cow milk possesses high nutritional value due to its rich array of beneficial fatty acids. It is important to understand the mechanisms involved in lipid metabolism in dairy cows. These mechanisms are driven by a complex molecular regulatory network. In addition, there are [...] Read more.
Cow milk possesses high nutritional value due to its rich array of beneficial fatty acids. It is important to understand the mechanisms involved in lipid metabolism in dairy cows. These mechanisms are driven by a complex molecular regulatory network. In addition, there are many regulatory factors involved in the process of fatty acid metabolism, including transcription factors and non-coding RNAs, amongst others. MicroRNAs (miRNAs) can regulate the expression of target genes and modulate various biological processes, including lipid metabolism. Specifically, miR-206 has been reported to impair lipid accumulation in nonruminant hepatocytes. However, the effects and regulatory mechanisms of miR-206 on lipid metabolism in bovine mammary cells remain unclear. In the present study, we investigated the effects of miR-206 on lipid-related genes and TAG accumulation. The direct downstream gene of miR-206 was subsequently determined via a dual-luciferase assay. Finally, the fatty acid content of bovine mammary epithelial cells (BMECs) upon ELOVL6 inhibition was examined. The results revealed that miR-206 overexpression significantly decreased triacylglycerol (TAG) concentration and abundances of the following: acetyl-coenzyme A carboxylase alpha (ACACA); fatty acid synthase (FASN); sterol regulatory element binding transcription factor 1 (SREBF1); diacylglycerol acyltransferase 1 (DGAT1); 1-acylglycerol-3-phosphate O-acyltransferase 6 (AGPAT6); lipin 1 (LPIN1); and fatty acid elongase 6 (ELOVL6). Overexpression of miR-206 was also associated with an increase in patatin-like phospholipase domain-containing 2 (PNPLA2), while inhibition of miR-206 promoted milk fat metabolism in vitro. In addition, we found that ELOVL6 is a direct target gene of miR-206 through mutation of the binding site. Furthermore, ELOVL6 intervention significantly decreased the TAG levels and elongation indexes of C16:0 and C16:1n-7 in BMECs. Finally, ELOVL6 siRNA partially alleviated the increased TAG accumulation caused by miR-206 inhibition. In summary, we found that miR-206 inhibits milk fatty acid synthesis and lipid accumulation by targeting ELOVL6 in BMECs. The results presented in this paper may contribute to the development of strategies for enhancing the quality of cow milk and its beneficial fatty acids, from the perspective of miRNA–mRNA networks. Full article
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32 pages, 5721 KiB  
Review
Elongation of Very Long-Chain Fatty Acids (ELOVL) in Atopic Dermatitis and the Cutaneous Adverse Effect AGEP of Drugs
by Markus Blaess, René Csuk, Teresa Schätzl and Hans-Peter Deigner
Int. J. Mol. Sci. 2024, 25(17), 9344; https://doi.org/10.3390/ijms25179344 - 28 Aug 2024
Viewed by 536
Abstract
Atopic dermatitis (AD) is a common inflammatory skin disease, in particular among infants, and is characterized, among other things, by a modification in fatty acid and ceramide composition of the skin’s stratum corneum. Palmitic acid and stearic acid, along with C16-ceramide [...] Read more.
Atopic dermatitis (AD) is a common inflammatory skin disease, in particular among infants, and is characterized, among other things, by a modification in fatty acid and ceramide composition of the skin’s stratum corneum. Palmitic acid and stearic acid, along with C16-ceramide and 2-hydroxy C16-ceramide, occur strikingly in AD. They coincide with a simultaneous decrease in very long-chain ceramides and ultra-long-chain ceramides, which form the outermost lipid barrier. Ceramides originate from cellular sphingolipid/ceramide metabolism, comprising a well-orchestrated network of enzymes involving various ELOVLs and CerSs in the de novo ceramide synthesis and neutral and acid CERase in degradation. Contrasting changes in long-chain ceramides and very long-chain ceramides in AD can be more clearly explained by the compartmentalization of ceramide synthesis. According to our hypothesis, the origin of increased C16-ceramide and 2-hydroxy C16-ceramide is located in the lysosome. Conversely, the decreased ultra-long-chain and very long-chain ceramides are the result of impaired ELOVL fatty acid elongation. The suggested model’s key elements include the lysosomal aCERase, which has pH-dependent long-chain C16-ceramide synthase activity (revaCERase); the NADPH-activated step-in enzyme ELOVL6 for fatty acid elongation; and the coincidence of impaired ELOVL fatty acid elongation and an elevated lysosomal pH, which is considered to be the trigger for the altered ceramide biosynthesis in the lysosome. To maintain the ELOVL6 fatty acid elongation and the supply of NADPH and ATP to the cell, the polyunsaturated PPARG activator linoleic acid is considered to be one of the most suitable compounds. In the event that the increase in lysosomal pH is triggered by lysosomotropic compounds, compounds that disrupt the transmembrane proton gradient or force the breakdown of lysosomal proton pumps, non-HLA-classified AGEP may result. Full article
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11 pages, 2994 KiB  
Article
Effects of Soybean Isoflavones on the Growth Performance and Lipid Metabolism of the Juvenile Chinese Mitten Crab Eriocheir sinensis
by Mengyu Shi, Yisong He, Jiajun Zheng, Yang Xu, Yue Tan, Li Jia, Liqiao Chen, Jinyun Ye and Changle Qi
Fishes 2024, 9(9), 335; https://doi.org/10.3390/fishes9090335 - 26 Aug 2024
Viewed by 418
Abstract
In order to study the effects of soybean isoflavones on the growth performance and lipid metabolism of juvenile Chinese mitten crabs, six experimental diets were formulated by gradient supplementation with 0%, 0.004% and 0.008% soybean isoflavones at different dietary lipid levels (10% and [...] Read more.
In order to study the effects of soybean isoflavones on the growth performance and lipid metabolism of juvenile Chinese mitten crabs, six experimental diets were formulated by gradient supplementation with 0%, 0.004% and 0.008% soybean isoflavones at different dietary lipid levels (10% and 15%). The groups were named as follows: NF-0 group (10% fat and 0% SIFs), NF-0.004 group (10% fat and 0.004% SIFs), NF-0.008 group (10% fat and 0.008% SIFs), HF-0 group (15% fat and 0% SIFs), HF-0.004 group (15% fat and 0.004% SIFs) and HF-0.008 group (15% fat and 0.008% SIFs). All crabs with an initial weight of 0.4 ± 0.03 g were fed for 8 weeks. The results showed that dietary supplementation with 0.004% or 0.008% SIFs significantly increased the weight gain and specific growth rate of crabs. Diets supplemented with 0.004% or 0.008% SIFs significantly reduced the content of non-esterified free fatty acids and triglycerides in the hepatopancreas of crabs at the 10% dietary lipid level. Dietary SIFs significantly decreased the relative mRNA expressions of elongase of very-long-chain fatty acids 6 (elovl6), triglyceride lipase (tgl), sterol regulatory element-binding protein 1 (srebp-1), carnitine palmitoyltransferase-1a (cpt-1a), fatty acid transporter protein 4 (fatp4), carnitine palmitoyltransferase-2 (cpt-2), Δ9 fatty acyl desaturase (Δ9 fad), carnitine palmitoyltransferase-1b (cpt-1b), fatty acid-binding protein 10 (fabp10) and microsomal triglyceride transfer protein (mttp) in the hepatopancreas of crabs. At the 15% dietary lipid level, 0.008% SIFs significantly increased the relative mRNA expressions of fatty acid-binding protein 3 (fabp3), carnitine acetyltransferase (caat), fatp4, fabp10, tgl, cpt-1a, cpt-1b and cpt-2 and significantly down-regulated the relative mRNA expressions of Δ9 fad and srebp-1. In conclusion, SIFs can improve the growth and utilization of a high-fat diet by inhibiting genes related to lipid synthesis and promoting lipid decomposition in juvenile Chinese mitten crabs. Full article
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15 pages, 4742 KiB  
Article
Molecular Identification and Functional Characterization of LC-PUFA Biosynthesis Elongase (elovl2) Gene in Chinese Sturgeon (Acipenser sinensis)
by Haoze Ding, Xuetao Shi, Zhengyong Wen, Xin Zhu, Pei Chen, Yacheng Hu, Kan Xiao, Jing Yang, Tian Tian, Dezhi Zhang, Shuqi Wang and Yang Li
Animals 2024, 14(16), 2343; https://doi.org/10.3390/ani14162343 - 14 Aug 2024
Viewed by 881
Abstract
Elongases of very-long-chain fatty acids (Elovls) are critical rate-limiting enzymes that are involved in LC-PUFA biosynthesis through catalyzing the two-carbon elongation of a pre-existing fatty acyl chain. Thus far, several Elovls have been extensively studied in teleost. However, the functional and physiological roles [...] Read more.
Elongases of very-long-chain fatty acids (Elovls) are critical rate-limiting enzymes that are involved in LC-PUFA biosynthesis through catalyzing the two-carbon elongation of a pre-existing fatty acyl chain. Thus far, several Elovls have been extensively studied in teleost. However, the functional and physiological roles of Elovls in chondrichthyans have rarely been reported. In this study, we identified and characterized elovl2 from the endangered Chinese sturgeon (Acipenser sinensis) by whole genome scanning. The results show that the coding sequence of elovl2 was 894 bp in length, for a putative protein of 297 amnio acids. Comparative genomic analyses indicated that Chinese sturgeon elovl2 was evolutionarily conserved. Functional characterization in yeast demonstrated that the Chinese sturgeon Elovl2 could efficiently elongate C20 (ARA and EPA) and C22 (22:4n-6 and 22:5n-3) substrates, confirming its critical roles in LC-PUFA biosynthesis. Spatial and temporal expression analyses showed high elovl2 mRNA levels were detected in the liver and brain and showed an increase trend both in embryonic and post-hatching stages. Interestingly, diets with vegetable oils as lipid sources could significantly induce the high expression of elovl2 in Chinese sturgeon, implying that the endogenous LC-PUFA biosynthesis pathway was stimulated by lack of LC-PUFA in their diets. Our findings will enhance our understanding about the evolutionary and functional roles of elovl2 and provide novel insights into the LC-PUFA biosynthesis mechanism in vertebrates. Full article
(This article belongs to the Section Aquatic Animals)
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15 pages, 4378 KiB  
Article
ELOVL2, PRKG2, and EDARADD DNA Methylation Strongly Estimate Indonesian Adolescents
by Nurtami Soedarsono, Muhammad Garry Syahrizal Hanafi, Bambang Tri Hartomo and Elza Ibrahim Auerkari
Diagnostics 2024, 14(16), 1767; https://doi.org/10.3390/diagnostics14161767 - 14 Aug 2024
Viewed by 538
Abstract
Recently, there has been a growing interest in using DNA methylation analysis for age estimation. Despite this growing interest, there is a scarcity of research on the potential of DNA methylation as a biomarker for age estimation in Indonesia. This study aims to [...] Read more.
Recently, there has been a growing interest in using DNA methylation analysis for age estimation. Despite this growing interest, there is a scarcity of research on the potential of DNA methylation as a biomarker for age estimation in Indonesia. This study aims to investigate the applicability of ELOVL2, PRKG2, and EDARADD genes for forensic identification in the 11–20 age group among Indonesians. This research utilizes 43 archived blood samples from healthy individuals who underwent blood tests at the Gatot Soebroto Army Hospital (RSPAD) in Central Jakarta, Indonesia. The methylation-specific PCR (MSP) technique assessed the DNA methylation level. The key findings of this study include (1) a strong positive correlation between methylation levels in the ELOVL2 gene and age; (2) a strong negative correlation between methylation levels in PRKG2 and EDARADD genes with age; (3) the development of three linear regression formulas for age prediction; and (4) mean absolute error (MAE) values derived from this research, which are ±0.48 for ELOVL2 gene regression formula, ±0.58 for PRKG2 gene regression formula, and ±0.72 for EDARADD gene regression formula. In summary, this study explores the potential of DNA methylation analysis for age estimation in Indonesia, focusing on ELOVL2, PRKG2, and EDARADD genes in the 11–20 age group. The findings underscore the applicability of DNA methylation analysis in forensic identification and age estimation, paving the way for future research in this field. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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17 pages, 1134 KiB  
Article
Physical Activity and Epigenetic Aging in Breast Cancer Treatment
by Chantalle Moulton, Elisa Grazioli, José Santiago Ibáñez-Cabellos, Arianna Murri, Claudia Cerulli, Monica Silvestri, Daniela Caporossi, Federico V. Pallardó, José Luis García-Giménez, Stefano Magno, Cristina Rossi, Guglielmo Duranti, Salvador Mena-Molla, Attilio Parisi and Ivan Dimauro
Int. J. Mol. Sci. 2024, 25(16), 8596; https://doi.org/10.3390/ijms25168596 - 6 Aug 2024
Viewed by 931
Abstract
Biological age, reflecting the cumulative damage in the body over a lifespan, is a dynamic measure more indicative of individual health than chronological age. Accelerated aging, when biological age surpasses chronological age, is implicated in poorer clinical outcomes, especially for breast cancer (BC) [...] Read more.
Biological age, reflecting the cumulative damage in the body over a lifespan, is a dynamic measure more indicative of individual health than chronological age. Accelerated aging, when biological age surpasses chronological age, is implicated in poorer clinical outcomes, especially for breast cancer (BC) survivors undergoing treatments. This preliminary study investigates the impact of a 16-week online supervised physical activity (PA) intervention on biological age in post-surgery female BC patients. Telomere length was measured using qPCR, and the ELOVL2-based epigenetic clock was assessed via DNA methylation pyrosequencing of the ELOVL2 promoter region. Telomere length remained unchanged, but the ELOVL2 epigenetic clock indicated a significant decrease in biological age in the PA group, suggesting the potential of PA interventions to reverse accelerated aging processes in BC survivors. The exercise group showed improved cardiovascular fitness, highlighting PA’s health impact. Finally, the reduction in biological age, as measured by the ELOVL2 epigenetic clock, was significantly associated with improvements in cardiovascular fitness and handgrip strength, supporting improved recovery. Epigenetic clocks can potentially assess health status and recovery progress in BC patients, identifying at-risk individuals in clinical practice. This study provides potential and valuable insights into how PA benefits BC survivors’ health, supporting the immediate benefits of a 16-week exercise intervention in mitigating accelerated aging. The findings could suggest a holistic approach to improving the health and recovery of post-surgery BC patients. Full article
(This article belongs to the Special Issue Skeletal Muscle Adaptations to Oxidative Stress)
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17 pages, 4921 KiB  
Article
Threonine Deficiency Increases Triglyceride Deposition in Primary Duck Hepatocytes by Reducing STAT3 Phosphorylation
by Zhong Zhuang, Wenqian Jia, Lei Wu, Yongpeng Li, Yijia Lu, Minghong Xu, Hao Bai, Yulin Bi, Zhixiu Wang, Shihao Chen, Yong Jiang and Guobin Chang
Int. J. Mol. Sci. 2024, 25(15), 8142; https://doi.org/10.3390/ijms25158142 - 26 Jul 2024
Viewed by 755
Abstract
Liver lipid metabolism disruption significantly contributes to excessive fat buildup in waterfowl. Research suggests that the supplementation of Threonine (Thr) in the diet can improve liver lipid metabolism disorder, while Thr deficiency can lead to such metabolic disorders in the liver. The mechanisms [...] Read more.
Liver lipid metabolism disruption significantly contributes to excessive fat buildup in waterfowl. Research suggests that the supplementation of Threonine (Thr) in the diet can improve liver lipid metabolism disorder, while Thr deficiency can lead to such metabolic disorders in the liver. The mechanisms through which Thr regulates lipid metabolism remain unclear. STAT3 (signal transducer and activator of transcription 3), a crucial transcription factor in the JAK-STAT (Janus kinase–signal transducer and activator of transcription) pathway, participates in various biological processes, including lipid and energy metabolism. This research investigates the potential involvement of STAT3 in the increased lipid storage seen in primary duck hepatocytes as a result of a lack of Thr. Using small interfering RNA and Stattic, a specific STAT3 phosphorylation inhibitor, we explored the impact of STAT3 expression patterns on Thr-regulated lipid synthesis metabolism in hepatocytes. Through transcriptome sequencing, we uncovered pathways related to lipid synthesis and metabolism jointly regulated by Thr and STAT3. The results showed that Thr deficiency increases lipid deposition in primary duck hepatocytes (p < 0.01). The decrease in protein and phosphorylation levels of STAT3 directly caused this deposition (p < 0.01). Transcriptomic analysis revealed that Thr deficiency and STAT3 knockdown jointly altered the mRNA expression levels of pathways related to long-chain fatty acid synthesis and energy metabolism (p < 0.05). Thr deficiency, through mediating STAT3 inactivation, upregulated ELOVL7, PPARG, MMP1, MMP13, and TIMP4 mRNA levels, and downregulated PTGS2 mRNA levels (p < 0.01). In summary, these results suggest that Thr deficiency promotes lipid synthesis, reduces lipid breakdown, and leads to lipid metabolism disorders and triglyceride deposition by downregulating STAT3 activity in primary duck hepatocytes. Full article
(This article belongs to the Special Issue Amino Acids and Related Compounds in Health and Disease)
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12 pages, 6504 KiB  
Article
Testosterone Inhibits Lipid Accumulation in Porcine Preadipocytes by Regulating ELOVL3
by Fuyin Xie, Yubei Wang, Shuheng Chan, Meili Zheng, Mingming Xue, Xiaoyang Yang, Yabiao Luo and Meiying Fang
Animals 2024, 14(15), 2143; https://doi.org/10.3390/ani14152143 - 23 Jul 2024
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Abstract
Castration is commonly used to reduce stink during boar production. In porcine adipose tissue, castration reduces androgen levels resulting in metabolic disorders and excessive fat deposition. However, the underlying detailed mechanism remains unclear. In this study, we constructed porcine preadipocyte models with and [...] Read more.
Castration is commonly used to reduce stink during boar production. In porcine adipose tissue, castration reduces androgen levels resulting in metabolic disorders and excessive fat deposition. However, the underlying detailed mechanism remains unclear. In this study, we constructed porcine preadipocyte models with and without androgen by adding testosterone exogenously. The fluorescence intensity of lipid droplet (LD) staining and the fatty acid synthetase (FASN) mRNA levels were lower in the testosterone-treated cells than in the untreated control cells. In contrast, the mRNA levels of adipose triglycerides lipase (ATGL) and androgen receptor (AR) were higher than in the testosterone-treated cells than in the control cells. Subsequently, transcriptomic sequencing of porcine preadipocytes incubated with and without testosterone showed that the mRNA expression levels of very long-chain fatty acid elongase 3 (ELOVL3), a key enzyme involved in fatty acids synthesis and metabolism, were high in control cells. The siRNA-mediated knockdown of ELOVL3 reduced LD accumulation and the mRNA levels of FASN and increased the mRNA levels of ATGL. Next, we conducted dual-luciferase reporter assays using wild-type and mutant ELOVL3 promoter reporters, which showed that the ELOVL3 promoter contained an androgen response element (ARE); furthermore, its transcription was negatively regulated by AR overexpression. In conclusion, our study reveals that testosterone inhibits fat deposition in porcine preadipocytes by suppressing ELOVL3 expression. Moreover, our study provides a theoretical basis for further studies on the mechanisms of fat deposition caused by castration. Full article
(This article belongs to the Section Pigs)
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30 pages, 4505 KiB  
Article
Prolonged Cold Exposure Negatively Impacts Atlantic Salmon (Salmo salar) Liver Metabolism and Function
by Isis Rojas, Albert Caballero-Solares, Émile Vadboncoeur, Rebeccah M. Sandrelli, Jennifer R. Hall, Kathy A. Clow, Christopher C. Parrish, Matthew L. Rise, Andrew K. Swanson and Anthony K. Gamperl
Biology 2024, 13(7), 494; https://doi.org/10.3390/biology13070494 - 3 Jul 2024
Viewed by 1044
Abstract
Large-scale mortality events have occurred during the winter in Atlantic salmon sea cages in Eastern Canada and Iceland. Thus, in salmon held at 3 °C that were apparently healthy (i.e., asymptomatic) and that had ‘early’ and ‘advanced’ symptoms of ‘winter syndrome’/’winter disease’ (WS/WD), [...] Read more.
Large-scale mortality events have occurred during the winter in Atlantic salmon sea cages in Eastern Canada and Iceland. Thus, in salmon held at 3 °C that were apparently healthy (i.e., asymptomatic) and that had ‘early’ and ‘advanced’ symptoms of ‘winter syndrome’/’winter disease’ (WS/WD), we measured hepatic lipid classes and fatty acid levels, and the transcript expression of 34 molecular markers of fatty liver disease (FLD; a clinical sign of WS/WD). In addition, we correlated our results with previously reported characteristics associated with this disease’s progression in these same individuals. Total lipid and triacylglycerol (TAG) levels increased by ~50%, and the expression of 32 of the 34 genes was dysregulated, in fish with symptoms of FLD. TAG was positively correlated with markers of inflammation (5loxa, saa5), hepatosomatic index (HSI), and plasma aspartate aminotransferase levels, but negatively correlated with genes related to lipid metabolism (elovl5b, fabp3a, cd36c), oxidative stress (catc), and growth (igf1). Multivariate analyses clearly showed that the three groups of fish were different, and that saa5 was the largest contributor to differences. Our results provide a number of biomarkers for FLD in salmon, and very strong evidence that prolonged cold exposure can trigger FLD in this ecologically and economically important species. Full article
(This article belongs to the Section Marine Biology)
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16 pages, 3844 KiB  
Article
Transcriptome Analysis Reveals the Potential Key Genes in Nutritional Deposition in the Common Carp (Cyprinus carpio)
by Yunya Wu, Pengfei Xiao, Hang Sha, Xiangzhong Luo, Guiwei Zou and Hongwei Liang
Animals 2024, 14(13), 1939; https://doi.org/10.3390/ani14131939 - 30 Jun 2024
Viewed by 717
Abstract
The common carp (Cyprinus carpio) is one of the most important aquaculture species in China, known for its remarkable adaptability and nutritional profile. However, the specific molecular response mechanisms regulating the nutritional deposition of carp remain inadequately elucidated. This study conducted [...] Read more.
The common carp (Cyprinus carpio) is one of the most important aquaculture species in China, known for its remarkable adaptability and nutritional profile. However, the specific molecular response mechanisms regulating the nutritional deposition of carp remain inadequately elucidated. This study conducted a comprehensive analysis of muscle nutritional content and transcriptome data from liver and muscle tissues of three distinct carp varieties. The aim was to elucidate the key genes and signaling pathways that regulate muscle nutritional composition in carp. The findings revealed that FFRC carp (FFRC) exhibited significantly higher levels of crude fat, total n-3 polyunsaturated fatty acids, and total n-6 polyunsaturated fatty acids in muscle tissue compared to Ying carp (YC) and Huanghe carp (HC) (p < 0.05). Transcriptomic analyses correlated these elevated levels with a marked upregulation of genes involved in the activation and transportation of fatty acid (fabp7, acsl5, acsbg2) as well as biosynthesis and elongation of long-chain unsaturated fatty acids (elovl2, fads2) within the liver. Furthermore, the flavor amino acid, essential amino acids, and crude protein content in the muscle of HC were significantly higher than in FFRC and YC (p < 0.05). Transcriptomic analyses indicated that this was associated with significant changes in the expression of genes related to amino acid metabolism (asns, alt, ldha, glul, setd, prodh, l3hypdh, hoga1) within their muscle tissue. This research provides a theoretical foundation for the precise modulation of the muscle nutritional composition in carp. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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