Flaxseed and Carbohydrase Enzyme Supplementation Alters Hepatic n-3 Polyunsaturated Fatty Acid Molecular Species and Expression of Genes Associated with Lipid Metabolism in Broiler Chickens

Flaxseed is rich in α-linolenic acid and is used in broiler chicken diets to enrich tissues with n-3 fatty acids (FA). However, non-starch polysaccharides (NSP) in flaxseed decreases nutrient digestibility and limits the availability of n-3 FA. Addition of carbohydrase enzymes to flaxseed-based diets can decrease the anti-nutritive effects of NSP. We hypothesized that flaxseed and enzyme supplementation affect lipid content and alter expression of genes related to lipid metabolism in broiler liver. Five day-old broiler chicks were fed a corn-soybean basal diet with 0% flaxseed, a basal diet with 10% of flaxseed, or 10% flaxseed + 0.05% enzyme diet up to day 42 of growth. Total lipids, including long-chain (≥20C) n-3 FA and monounsaturated FA, were increased in flax-fed broiler livers. Enzyme addition reduced arachidonic acid and total long chain n-6 FA. These changes were similarly reflected in phosphatidylcholine lipid species. Dietary flax and enzyme treatments up-regulated PPARα target genes CPT1A and ACOX1 while reducing expression of de novo FA synthesis-related genes. This study concludes that flaxseed and enzyme supplementation in broiler diets enhances LC n-3 FA species, while reducing n-6 FA species in hepatic phospholipids (PL). Flaxseed-based diets changes the expression of genes involved in FA lipid metabolism without affecting growth or production performance in broilers.

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Fine metabolic regulation in ruminants via nutrient–gene interactions: saturated long-chain fatty acids increase expression of genes involved in lipid metabolism and immune response partly through PPAR-α activation

British Journal Of Nutrition ◽

10.1017/s0007114511002777 ◽

2011 ◽

Vol 107 (2) ◽

pp. 179-191 ◽

Cited By ~ 52

Author(s):

Massimo Bionaz ◽

Betsy J. Thering ◽

Juan J. Loor

Keyword(s):

Fatty Acids ◽

Lipid Metabolism ◽

Metabolic Regulation ◽

Target Genes ◽

Long Chain Fatty Acids ◽

Response Data ◽

Expression Of Genes ◽

Gene Network Analysis ◽

Long Chain ◽

Chain Fatty Acids

Madin–Darby Bovine Kidney cells cultured with 150 μm of Wy-14 643 (WY, PPARα agonist) or twelve long-chain fatty acids (LCFA; 16 : 0, 18 : 0, cis-9–18 : 1, trans-10–18 : 1, trans-11–18 : 1, 18 : 2n-6, 18 : 3n-3, cis-9, trans-11–18 : 2, trans-10, cis-12–18 : 2, 20 : 0, 20 : 5n-3 and 22 : 6n-3) were used to uncover PPAR-α target genes and determine the effects of LCFA on expression of thirty genes with key functions in lipid metabolism and inflammation. Among fifteen known PPAR-α targets in non-ruminants, ten had greater expression with WY, suggesting that they are bovine PPAR-α targets. The expression of SPP1 and LPIN3 was increased by WY, with no evidence of a similar effect in the published literature, suggesting that both represent bovine-specific PPAR-α targets. We observed the strongest effect on the expression of PPAR-α targets with 16 : 0, 18 : 0 and 20 : 5n-3.When considering the overall effect on expression of the thirty selected genes 20 : 5n-3, 16 : 0 and 18 : 0 had the greatest effect followed by 20 : 0 and c9t11–18 : 2. Gene network analysis indicated an overall increase in lipid metabolism by WY and all LCFA with a central role of PPAR-α but also additional putative transcription factors. A greater increase in the expression of inflammatory genes was observed with 16 : 0 and 18 : 0. Among LCFA, 20 : 5n-3, 16 : 0 and 18 : 0 were the most potent PPAR-α agonists. They also affected the expression of non-PPAR-α targets, eliciting an overall increase in the expression of genes related to lipid metabolism, signalling and inflammatory response. Data appear to highlight a teleological evolutionary adaptation of PPAR in ruminants to cope with the greater availability of saturated rather than unsaturated LCFA.

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Long-chain acyl-CoA esters as indicators of lipid metabolism and insulin sensitivity in rat and human muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2000.279.3.e554 ◽

2000 ◽

Vol 279 (3) ◽

pp. E554-E560 ◽

Cited By ~ 146

Author(s):

Bronwyn A. Ellis ◽

Ann Poynten ◽

Andrew J. Lowy ◽

Stuart M. Furler ◽

Donald J. Chisholm ◽

...

Keyword(s):

Adipose Tissue ◽

Lipid Metabolism ◽

Insulin Action ◽

Human Muscle ◽

Whole Body ◽

Cellular Processes ◽

Lipid Species ◽

Chain Acyl ◽

Triglyceride Content ◽

Long Chain

Long-chain acyl-CoAs (LCACoA) are an activated lipid species that are key metabolites in lipid metabolism; they also have a role in the regulation of other cellular processes. However, few studies have linked LCACoA content in rat and human muscle to changes in nutritional status and insulin action. Fasting rats for 18 h significantly elevated the three major LCACoA species in muscle ( P < 0.001), whereas high-fat feeding of rats with a safflower oil (18:2) diet produced insulin resistance and increased total LCACoA content ( P < 0.0001) by specifically increasing 18:2-CoA. The LCACoA content of red muscle from rats (4–8 nmol/g) was 4- to 10-fold higher than adipose tissue (0.4–0.9 nmol/g, P < 0.001), suggesting that any contamination of muscle samples with adipocytes would contribute little to the LCACoA content of muscle. In humans, the LCACoA content of muscle correlated significantly with a measure of whole body insulin action in 17 male subjects ( r 2 = 0.34, P = 0.01), supporting a link between muscle lipid metabolism and insulin action. These results demonstrate that the LCACoA pool reflects lipid metabolism and nutritional state in muscle. We conclude that the LCACoA content of muscle provides a direct index of intracellular lipid metabolism and its links to insulin action, which, unlike triglyceride content, is not subject to contamination by closely associated adipose tissue.

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2,4-Dinitrotoluene (DNT) Perturbs Yolk Absorption, Liver Development and Lipid Metabolism/Oxygen Transport Gene Expression in Zebrafish Embryos and Larvae

International Journal of Molecular Sciences ◽

10.3390/ijms20153632 ◽

2019 ◽

Vol 20 (15) ◽

pp. 3632

Author(s):

Jianglin Xiong ◽

Hang Sha ◽

Hualin Zhou ◽

Lijuan Peng ◽

Lingying Wu ◽

...

Keyword(s):

Gene Expression ◽

Lipid Metabolism ◽

Oxygen Transport ◽

Target Genes ◽

Environmental Pollutant ◽

International Agency ◽

Liver Development ◽

Expression Of Genes ◽

Yolk Absorption ◽

Carcinogenic Compound

2,4-dinitrotoluene (2,4-DNT) is a common environmental pollutant, and was classified as a group 2B human carcinogenic compound by the International Agency for Research on Cancer. This study determined the toxic effects of 2,4-DNT exposure on zebrafish at the embryo-larvae stage, in terms of organ morphogenesis and the expression pattern of selected target genes related to lipid metabolism and oxygen transportation. The results showed that the 120-h post-fertilization LC50 of 2,4-DNT was 9.59 mg/L with a 95% confidence interval of 8.89–10.44 mg/L. The larvae treated with 2,4-DNT showed toxic symptoms including smaller body, less skin pigment production, yolk malabsorption, and disordered liver development. Further studies on the expression of genes related to lipid transport and metabolism, and respiration indicated that they were significantly affected by 2,4-DNT. It is concluded that 2,4-DNT exposure perturbed liver development and yolk absorption in early-life zebrafish, and disturbed the lipid metabolism /oxygen transport gene expression.

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Assisted reproduction causes intrauterus growth restriction by disrupting placental lipid metabolism

10.1101/030965 ◽

2015 ◽

Cited By ~ 1

Author(s):

Yubao Wei ◽

Shuqiang Chen ◽

Xiuying Huang ◽

Sin Man Lam ◽

Guanghou Shui ◽

...

Keyword(s):

Lipid Metabolism ◽

Growth Restriction ◽

Imprinted Genes ◽

Lipid Uptake ◽

Vitro Fertilization ◽

Metabolism Regulation ◽

Expression Of Genes ◽

Lipid Species

IVF related intrauterus growth restriction or low birth weight (LBW) is very common in ART clinic. This study is focus on the aberrant lipid metabolism induced by in vitro fertilization and its mechanism. Firstly, we investigated the effect of IVF on fetal weight and placenta efficiency at E18.5 (at birth) and E14.5 (middle gestation). Data shows that IVF caused LBW and low placenta efficiency. Then we studied the lipidomics of E18.5 placenta and E14.5 placenta. The IVF group has an eccentric lipid content compared to in vivo group. All the 15 lipid classes are largely accumulated in E18.5 IVF placenta and are deficient in E14.5 IVF placenta. In detail, most of the 287 lipid species is accumulated at E18.5 and went short at E14.5. Using qRT-PCR we detected the expression level of genes related to lipid uptake, transport and metabolism. Most of these genes are down-regulated which indicated the metabolism function of placenta is disrupted seriously. To the imprinted genes for lipid metabolism regulation as GNAS and Grb10, IVF not only disrupt their imprinting status (methylation level) but also disrupt their gene expression. The expression of DNMTs and Tets are also disrupted in the placenta. These data demonstrate that IVF impaired the regulation network of lipid metabolism. These results prove the hypothesis: imperfect IVF condition of fertilization jeopardize the expression DNMTs, Tets and imprinting status of imprinted genes for lipid metabolism regulation. Then it causes to abnormal expression of genes for lipid metabolism and regulation. This leads to the significant differences in lipid species quantification and lipid metabolism. So it contributed to low lipid transport efficiency, restricted fetal growth and LBW. This study provides a renewed knowledge of lipid metabolism in placenta and its relation to imprinted genes and gave some clinical aware for optimizing the ART practice.

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Analysis and Functional Verification of PoWRI1 Gene Associated with Oil Accumulation Process in Paeonia ostii

International Journal of Molecular Sciences ◽

10.3390/ijms22136996 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6996

Author(s):

Jing Sun ◽

Tian Chen ◽

Mi Liu ◽

Daqiu Zhao ◽

Jun Tao

Keyword(s):

Transcription Factor ◽

Fatty Acid ◽

Target Genes ◽

De Novo ◽

Fatty Acid Content ◽

Functional Verification ◽

Oil Accumulation ◽

Reading Frame ◽

Downstream Target ◽

Expression Of Genes

The plant transcription factor WRINKLED1 (WRI1), a member of AP2/EREBP, is involved in the regulation of glycolysis and the expression of genes related to the de novo synthesis of fatty acids in plastids. In this study, the key regulator of seed oil synthesis and accumulation transcription factor gene PoWRI1 was identified and cloned, having a complete open reading frame of 1269 bp and encoding 422 amino acids. Subcellular localization analysis showed that PoWRI1 is located at the nucleus. After the expression vector of PoWRI1 was constructed and transformed into wild-type Arabidopsis thaliana, it was found that the overexpression of PoWRI1 increased the expression level of downstream target genes such as BCCP2, KAS1, and PKP-β1. As a result, the seeds of transgenic plants became larger, the oil content increased significantly, and the unsaturated fatty acid content increased, which provide a scientific theoretical basis for the subsequent use of genetic engineering methods to improve the fatty acid composition and content of plant seeds.

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Dietary calcium supplementation affects nutrient digestibility and antler-production performance during the antler-velvet growth period of male sika deer

Animal Production Science ◽

10.1071/an17862 ◽

2019 ◽

Vol 59 (9) ◽

pp. 1689

Author(s):

Weili Sun ◽

Haiping Zhao ◽

Kun Bao ◽

Chunyi Li ◽

Guangyu Li

Keyword(s):

Sika Deer ◽

Calcium Supplementation ◽

Growth Period ◽

Basal Diet ◽

Optimal Level ◽

Nutrient Digestibility ◽

Production Performance ◽

The Other ◽

Feed Digestibility ◽

Antler Growth

Effects of calcium (Ca) supplementation on nutrient digestibility, physiochemical characteristics and antler growth in farmed male sika deer were investigated. Eighteen sika deer (6 years old, 105.50 ± 5.05 kg) were assigned into the following three treatments where they had ad libitum access to water for 90 days: (1) control (C), basal diet containing 0.5% Ca; (2) Ca1.10, basal diet supplemented with 0.6% Ca; and (3) Ca1.70, basal diet supplemented with 1.2% Ca. The basal diet contained 0.50% Ca and 0.34% phosphorus (P). Each group consisted of the same ratio of Ca to P (provided as CaCO3 and CaHPO4). The results showed that the digestibility of dry matter (DM) and crude protein in the Ca1.70 group was lower than in the other two groups. The digestibilities of Ca, P and neutral detergent fibre in the Ca1.10 group were higher than those in the C group and Ca1.70 group (P < 0.05). Concentrations of Ca and P in faeces increased with an increasing supplementation level of Ca and the highest concentrations were observed in the Ca1.70 group (P < 0.05). There were no differences in the concentrations of parathyroid hormone, alkaline phosphatase and osteocalcin among the treatments. Testosterone and oestradiol concentrations of the Ca1.7 group were higher than those of the C and Ca1.10 groups (P < 0.05). Average daily gains of fresh antler weight and dry antler weight of the groups Ca1.10 and Ca1.70 were greater than those of the C (P < 0.05). Fresh and dry antler yields of the Ca1.10 group were higher than those of the other groups (P < 0.05). In conclusion, optimal level of Ca supplement was found to be total Ca concentration of 1.10–1.70%, on the basis of DM, which significantly increased feed digestibility and antler daily gain for the 6-year-old sika deer.

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BIOL-10. DISTRIBUTION AND VULNERABILITY OF TRANSCRIPTIONAL OUTPUTS ACROSS THE GENOME IN MYC-AMPLIFIED MEDULLOBLASTOMA CELLS

Neuro-Oncology ◽

10.1093/neuonc/noab090.017 ◽

2021 ◽

Vol 23 (Supplement_1) ◽

pp. i5-i5

Author(s):

Rui Yang ◽

Wenzhe Wang ◽

Meichen Dong ◽

Kristen Roso ◽

Xuhui Bao ◽

...

Keyword(s):

Tumor Cells ◽

Target Genes ◽

De Novo ◽

Inhibitory Effect ◽

Nucleotide Synthesis ◽

Expression Of Genes ◽

High Level ◽

The Impact

Abstract Myc plays a central role in tumorigenesis by orchestrating the expression of genes essential to numerous cellular processes. While it is well established that Myc functions by binding to its target genes to regulate their transcription, the distribution of the transcriptional output across human genome in Myc-amplified cancer cells, and the susceptibility of such transcriptional outputs to therapeutic interferences remain to be fully elucidated. Here, we analyze the distribution of transcriptional outputs in Myc-amplified medulloblastoma (MB) cells by profiling nascent total RNAs within a temporal context. This profiling reveals a major portion of transcriptional action in these cells was directed at the genes fundamental to cellular infrastructures, including rRNAs and particularly those in the mitochondrial genome (mtDNA). Notably, even when Myc protein was depleted by as much as 80%, the impact on transcriptional outputs across the genome was limited, with notable reduction mostly in genes of involved in ribosomal biosynthesis, genes residing in mtDNA or encoding mitochondria-localized proteins, and those encoding histones. In contrast to the limited direct impact of Myc depletion, we found that the global transcriptional outputs were highly dependent on the activity of Inosine Monophosphate Dehydrogenases (IMPDHs), rate limiting enzymes for de novo guanine nucleotide synthesis and whose expression in tumor cells was positively correlated with Myc’s expression. Blockage of IMPDHs attenuated the global transcriptional outputs with a particularly strong inhibitory effect on the aforementioned infrastructure genes, which was accompanied by the abrogation of MB cell’s proliferation in vitro and in vivo. Together, our findings reveal a real time action of Myc as a transcriptional factor in tumor cells, gain new insight into the pathogenic mechanism underlying Myc-driven tumorigenesis, and support IMPDHs as a therapeutic vulnerability in MB cells empowered by a high level of Myc oncoprotein.

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Role of lipids on elongation of the preimplantation conceptus in ruminants

Reproduction ◽

10.1530/rep-16-0104 ◽

2016 ◽

Vol 152 (4) ◽

pp. R115-R126 ◽

Cited By ~ 26

Author(s):

Eduardo S Ribeiro ◽

José E P Santos ◽

William W Thatcher

Keyword(s):

Fatty Acids ◽

Lipid Metabolism ◽

Cell Biology ◽

De Novo ◽

Dynamic Changes ◽

Expression Of Genes ◽

Trophectoderm Cells ◽

Conceptus Development ◽

Elongation Phase

Elongation of the preimplantation conceptus is a prerequisite for successful pregnancy in ruminants and depends on histotroph secretion by the endometrium. Lipids are an essential component of the histotroph, and recent studies indicate that lipids have important roles in the elongation phase of conceptus development. The onset of elongation is marked by dynamic changes in the transcriptome of trophectoderm cells, which are associated with lipid metabolism. During elongation, the trophectoderm increases transcript expression of genes related to uptake, metabolism andde novobiosynthesis of fatty acids and prostaglandins. Expression of the genePPARGincreases substantially, and activation of the transcription factor PPARG by binding of lipid ligands appears to be crucial for the coordination of cell biology during elongation. Lipids accumulated in the epithelial cells of the endometrium during diestrus are likely the most important source of fatty acids for utilization by the conceptus and become available in the uterine lumen through exporting of exosomes, microvesicles, carrier proteins and lipoproteins. Targeting of uterine lipid metabolism and PPARG activity during preimplantation conceptus development through nutraceutical diets may be a good strategy to improve pregnancy survival and reproductive efficiency in ruminants.

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Dietary Supplementation with Compound Probiotics and Berberine Alters Piglet Production Performance and Fecal Microbiota

Animals ◽

10.3390/ani10030511 ◽

2020 ◽

Vol 10 (3) ◽

pp. 511

Author(s):

Xiaoxiang Xu ◽

Canyu Yang ◽

Juan Chang ◽

Ping Wang ◽

Qingqiang Yin ◽

...

Keyword(s):

Average Daily Gain ◽

Dietary Supplementation ◽

Basal Diet ◽

Fecal Microbiota ◽

Diet Group ◽

Nutrient Digestibility ◽

Production Performance ◽

Control Group ◽

Feed Conversion ◽

Relative Abundances

This study was conducted to investigate the effects of dietary supplementation with compound probiotics and berberine (CPB) on growth performance, nutrient digestibility and fecal microflora in weaned piglets. A total of 200 piglets 35 days old were randomly allocated to 5 groups, 4 replications in each group, and 10 piglets in each replication. Group A was the basal diet; group B was supplemented with antibiotics and zinc oxide; groups C, D and E were supplemented with 0.06%, 0.12% and 0.18% CPB, respectively. The experimental period was 42 d. The results indicated that there were no significant differences in average daily feed intake (ADFI), average daily gain (ADG) and feed conversion rate (FCR) among five groups (p > 0.05). However, mortality, diarrhea and rejection rates in the control group were higher than that in other groups. CPB could increase protein digestibility and serum IgG content (p < 0.05), while it could decrease serum urea nitrogen content and alkaline phosphatase activity (p < 0.05). Analysis of fecal microbiota showed that the relative abundances of Bacteroides and Firmicutes were increased, while the relative abundances of opportunistic pathogens such as Spirochaetae and Protebactreria were dramatically decreased in piglets fed with CPB or antibiotics, compared with the control group. Furthermore, CPB intervention increased the relative abundances of Prevotella_9, Megasphaera and Prevotella_2, while decreased the relative abundance of Prevotellaceae_NK3B31_group. Correlation analysis revealed that there was good correlation between serum indexes and fecal microbiota. It was suggested that CPB might be a promising antibiotic alternative for improving piglet health and immunity, decreasing mortality by positively altering gut microbiota.

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Differential Expression of TCF3 Target Genes Defines Subclasses of Diffuse Large B-Cell Lymphoma with Striking Differences in Clinical Outcome Following R-CHOP Therapy

Blood ◽

10.1182/blood.v128.22.3037.3037 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3037-3037 ◽

Cited By ~ 1

Author(s):

Kathrin Tyryshkin ◽

Yi D Li ◽

David Good ◽

Lois E. Shepherd ◽

Tara Baetz ◽

...

Keyword(s):

B Cell ◽

Differential Expression ◽

Target Genes ◽

De Novo ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Expression Of Genes ◽

Pre Treatment ◽

Differential Expression Of Genes ◽

Chop Therapy

Abstract Background: Diffuse large B-cell lymphoma (DLBCL) is clinically and biologically heterogeneous. Whereas most patients are cured following conventional therapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), a substantial minority are refractory or relapse. Identifying patients at high risk of poor outcomes at the time of diagnosis will make it possible to better choose alternative or experimental therapies. TCF3 (also called E2A) is a transcription factor required in B-lymphopoiesis. Gain-of-function somatic mutations that alter TCF3 or its regulatory partners are associated withBurkitt lymphoma (BL) but not DLBCL. These published findings suggest that biologically-defined, clinically-important subtypes of mature B-cell-derived lymphomas may be distinguished from one another based on differential expression of genes regulated by a master regulator of B-lymphoid biology, namely TCF3. Therefore, in the current study, we hypothesized that biologically- and clinically-important subtypes of DLBCL are distinguishable based upon differential expression of genes that are regulated in B-cells by TCF3. Methods: Fifty-nine subjects who presented with de novo DLBCL at Kingston General Hospital from 2001 to 2010 were identified for inclusion based on the availability of clinical data and sufficient biopsy material for extraction of adequate RNA. We used publically-available microarray-based gene expression and clinical data to identify 99 candidate TCF3 target genes whose differential expression was associated with 3-year overall survival following R-CHOP therapy; these transcripts were represented in aNanoStringCodeSet. Total RNA was purified from cores harvested from representative areas of diagnostic, pre-treatment, formaldehyde-fixed, paraffin-embedded (FFPE) biopsy samples. Twenty-five transcripts whose abundance, individually, was associated with 3-year overall survival in our own cohort were chosen for further study. Results: Unsupervised hierarchical cluster analysis based on relative expression of the 25 TCF3 target genes resolved all except two cases into distinct clusters, denoted A and B, that contained 21 and 36 cases, respectively (heat map at left). In comparing these clusters, Cluster B was associated with rearrangement of MYC (p=0.02) as determined by FISH; no statistically significant associations were evident with age, sex, IPI score, B-symptoms, bulky disease or expression of MYC or BCL2 as determined by immunohistochemistry. Kaplan Meyer (KM) analysis revealed strikingly inferior overall and event-free survival (p=0.0005 for each) for Cluster A cases (KM curve at right). Conclusions: Our findings demonstrate that differential expression of TCF3 target genes ascertained in pre-treatment FFPE biopsy samples of de novo DLBCL defines biologically distinctive subsets of cases with distinctive clinical outcomes following R-CHOP therapy. If validated in an independent cohort, these results may inform both clinical management and the development of new targeted therapies for high-risk cases. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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