Effects of Isochronal Induced Feed Restriction With Transition Period On mRNA Abundance of The Hepatic Genes Related to Lipid Metabolism in Fat-Tailed Ewes

Abstract The process of fat mobilization during the transition period requires deep re-orchestration of the energy indices, and understanding its mechanism has generated considerable interest among the TP-related studies. The present study aims to validate the effect of feed restriction and TP on the mRNA abundance of hepatic genes related to fat metabolism in fat-tailed sheep. Twenty pregnant ewes with the age of 40.8 ± 6.2 (mean ± standard error) month were randomly assigned to Control (n=10) or Restriction (n=10), and investigated from week -5 to 5 relative to parturition. Control animals received 100% DM during the trial. Restriction animals received 100% DM through weeks -5, -1, 1 and 5 and were fed with 50, 65, and 80% DM in the weeks -4, -3, -2 and 2,3, and 4, respectively. On the third week of experiment (65%) during both pre and post-partum, the hepatic tissue was biopsied, and the mRNA load of the fatty acid synthase, acetyl-CoA carboxylase, carnitine palmitoyltransferase (CPT) 1, CPT2, and acyl-CoA synthase long-chain family member-1 genes was quantified by the TaqMan qPCR technique. Data were analyzed using the Mixed Model procedure of SAS. The mRNA abundance of the target genes was not influenced by feed restriction, during the pre and postpartum periods. Parturition suppressed the mRNA abundance of target genes in both groups. It can be concluded that the liver of the fat-tailed sheep would have a higher capacity for the metabolism of free fatty acids mobilization during the feed insufficiency and the challenging period of transition.

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PSXIII-36 The inflammatory response in cellular level changes during the transition period in dromedary camel

Journal of Animal Science ◽

10.1093/jas/skz258.736 ◽

2019 ◽

Vol 97 (Supplement_3) ◽

pp. 369-369

Author(s):

Mousa Zarrin ◽

Rachael Christensen ◽

S Kazem DoostMohammadi ◽

Ahmadali Ahmadpour ◽

Amir Ahmadpour

Keyword(s):

Oxidative Stress ◽

Transition Period ◽

Cellular Level ◽

Mrna Abundance ◽

Hepatic Tissue ◽

Dromedary Camel ◽

Free Access ◽

Initiation Time ◽

Dromedary Camels ◽

Access To Water

Abstract During the physiological transition around calving, many aspects of innate and acquired defence are suboptimal. Liver antioxidants would be expected to fluctuate during this time and could be affected by Nrf2 through some means of regulation. However, there is a lack of data on the initiation time of such defence systems against oxidative stress around calving in dromedary camels. Therefore, this study aimed to investigate the changes in expression of the responsible genes in the metabolism of antioxidant factors in hepatic tissue of camels at parturition. We studied ten multiparous (2.38 ± 0.56; mean parity) pregnant camels weighing 527.94 ± 73.46 kg BW during four months around parturition. Camels were pastured during the day, kept in individual stalls during the night, and provided with partial mixed ration and free access to water in the stalls. The mRNA abundance of Superoxide dismutase (SOD), Glutathione peroxidase (GPx), and Peroxiredoxin (Prx) were studied in the hepatic tissues from biopsies obtained at days 60, 45, 30, and 15 antepartum (AP) and days 3, 15, 30, 45, and 60 postpartum (PP), using qPCR technique. Compared to d 60AP, mRNA abundance of SOD1, GPx3, and also Prx1 (P = 0.05), remained unchanged. mRNA of the SOD3 reached a peak at d 3PP (P = 0.01), declined gradually until d 45PP and remained at that level until the experiment’s end. However, the abundance of GPx4 mRNA did not change from d 60AP until d 30PP, then decreased marginally, and stayed at that level to d 60 PP. GPx4 was significantly lower from d 30 to 60PP compared to d 3PP (P ≤ 0.05). These results may help substantiate the increased expression of Nrf2 during this period. Nrf2 could be considered as a primary immunoregulatory factor for orchestrating the genes responsible for cytoprotective systems against oxidative stress.

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The functional relationship between co-repressor N-CoR and SMRT in mediating transcriptional repression by thyroid hormone receptor α

Biochemical Journal ◽

10.1042/bj20071393 ◽

2008 ◽

Vol 411 (1) ◽

pp. 19-26 ◽

Cited By ~ 11

Author(s):

Kyung-Chul Choi ◽

So-Young Oh ◽

Hee-Bum Kang ◽

Yoo-Hyun Lee ◽

Seungjoo Haam ◽

...

Keyword(s):

Thyroid Hormone ◽

Hormone Receptor ◽

Transcriptional Repression ◽

Fatty Acid Synthase ◽

Hormone Receptors ◽

Target Genes ◽

Functional Relationship ◽

Thyroid Hormone Receptor ◽

B Cell Lymphoma ◽

Hormone Response Elements

A central issue in mediating repression by nuclear hormone receptors is the distinct or redundant function between co-repressors N-CoR (nuclear receptor co-repressor) and SMRT (silencing mediator of retinoid and thyroid hormone receptor). To address the functional relationship between SMRT and N-CoR in TR (thyroid hormone receptor)-mediated repression, we have identified multiple TR target genes, including BCL3 (B-cell lymphoma 3-encoded protein), Spot14 (thyroid hormone-inducible hepatic protein), FAS (fatty acid synthase), and ADRB2 (β-adrenergic receptor 2). We demonstrated that siRNA (small interfering RNA) treatment against either N-CoR or SMRT is sufficient for the de-repression of multiple TR target genes. By the combination of sequence mining and physical association as determined by ChIP (chromatin immunoprecipitation) assays, we mapped the putative TREs (thyroid hormone response elements) in BCL3, Spot14, FAS and ADRB2 genes. Our data clearly show that SMRT and N-CoR are independently recruited to various TR target genes. We also present evidence that overexpression of N-CoR can restore repression of endogenous genes after knocking down SMRT. Finally, unliganded, co-repressor-free TR is defective in repression and interacts with a co-activator, p300. Collectively, these results suggest that both SMRT and N-CoR are limited in cells and that knocking down either of them results in co-repressor-free TR and consequently de-repression of TR target genes.

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Regulation of the SREBP transcription factors by mTORC1

Biochemical Society Transactions ◽

10.1042/bst0390495 ◽

2011 ◽

Vol 39 (2) ◽

pp. 495-499 ◽

Cited By ~ 42

Author(s):

Caroline A. Lewis ◽

Beatrice Griffiths ◽

Claudio R. Santos ◽

Mario Pende ◽

Almut Schulze

Keyword(s):

Fatty Acid ◽

Fatty Acid Synthase ◽

Target Genes ◽

De Novo ◽

Regulatory Element ◽

Cholesterol Biosynthesis ◽

Mammalian Target Of Rapamycin ◽

Lipid Biosynthesis ◽

De Novo Lipogenesis ◽

Genes Encoding

In recent years several reports have linked mTORC1 (mammalian target of rapamycin complex 1) to lipogenesis via the SREBPs (sterol-regulatory-element-binding proteins). SREBPs regulate the expression of genes encoding enzymes required for fatty acid and cholesterol biosynthesis. Lipid metabolism is perturbed in some diseases and SREBP target genes, such as FASN (fatty acid synthase), have been shown to be up-regulated in some cancers. We have previously shown that mTORC1 plays a role in SREBP activation and Akt/PKB (protein kinase B)-dependent de novo lipogenesis. Our findings suggest that mTORC1 plays a crucial role in the activation of SREBP and that the activation of lipid biosynthesis through the induction of SREBP could be part of a regulatory pathway that co-ordinates protein and lipid biosynthesis during cell growth. In the present paper, we discuss the increasing amount of data supporting the potential mechanisms of mTORC1-dependent activation of SREBP as well as the implications of this signalling pathway in cancer.

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Glucose stimulates transcription of fatty acid synthase and malic enzyme in avian hepatocytes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1998.274.3.e493 ◽

1998 ◽

Vol 274 (3) ◽

pp. E493-E501 ◽

Cited By ~ 2

Author(s):

F. Bradley Hillgartner ◽

Tina Charron

Keyword(s):

Fatty Acid ◽

High Fat Diet ◽

Malic Enzyme ◽

Fatty Acid Synthase ◽

Primary Cultures ◽

Pentose Phosphate ◽

Mrna Abundance ◽

Low Fat Diet ◽

Low Carbohydrate

Transcription of fatty acid synthase (FAS) and malic enzyme (ME) in avian liver is low during starvation or feeding a low-carbohydrate, high-fat diet and high during feeding a high-carbohydrate, low-fat diet. The role of glucose in the nutritional control of FAS and ME was investigated by determining the effects of this metabolic fuel on expression of FAS and ME in primary cultures of chick embryo hepatocytes. In the presence of triiodothyronine, glucose (25 mM) stimulated an increase in the activity and mRNA abundance of FAS and ME. These effects required the phosphorylation of glucose to glucose 6-phosphate but not further metabolism downstream of the aldolase step of the glycolytic pathway. Xylitol mimicked the effects of glucose on FAS and ME expression, suggesting that an intermediate of the pentose phosphate pathway may be involved in mediating this response. The effects of glucose on the mRNA abundance of FAS and ME were accompanied by similar changes in transcription of FAS and ME. These data support the hypothesis that glucose plays a role in mediating the effects of nutritional manipulation on transcription of FAS and ME in liver.

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Effect of residual feed intake phenotype–nutritional treatment interaction on the growth performance, plasma metabolic variables and somatotropic axis gene expression of growing ewes

Animal Production Science ◽

10.1071/an14700 ◽

2016 ◽

Vol 56 (10) ◽

pp. 1593 ◽

Cited By ~ 1

Author(s):

H. T. Nie ◽

Z. Y. Wang ◽

S. Lan ◽

H. Zhang ◽

Y. J. Wan ◽

...

Keyword(s):

Gene Expression ◽

Growth Hormone ◽

Growth Performance ◽

Feed Intake ◽

Mrna Abundance ◽

Feed Restriction ◽

Somatotropic Axis ◽

Nutritional Treatment ◽

Treatment Interaction ◽

Ad Libitum

This study aimed to evaluate the effect of residual feed intake (RFI) phenotype and nutritional treatment interaction on the growth performance, plasma variables and gene expression levels within the somatotropic axis. Growing ewes [n = 52, initial bodyweight (BW) = 17.5 ± 0.5 kg, 2 months of age] were offered ad libitum access to diets for 63 days and ranked based on RFI phenotype. Thirty ewes with the highest and lowest RFI values were selected and randomly assigned to three nutritional treatments based on dry matter intake (DMI), which are ad libitum (AL), low restriction (LR) and high restriction (HR) groups, respectively. Each nutritional treatment group included ewes with high (n = 5) and low RFI (n = 5) values. During nutritional treatment (from Day 64 to Day 138), plasma samples were obtained to measure metabolite and hormone concentrations. Tissues of the hypothalamus, pituitary, liver, and Longissimus dorsi muscle (LM) were harvested at the end of the experiment (Day 138) to measure the gene expression level within the somatotropic axis. Muscle growth hormone receptor mRNA abundance of low RFI ewes tended to be greater (P = 0.09) under AL feeding, but this difference was abolished by underfeeding (P > 0.10). Low RFI ewes under HR treatment showed slightly greater growth performance, which was accompanied with lower pituitary somatostain receptor 2 mRNA abundance (P < 0.05), plasma non-esterified fatty acid concentration (P < 0.05), and greater concentration of triglyceride (P < 0.05), compared with ewes classified as high RFI group. Our results suggested that ewes categorised as low RFI showed higher resistance to the condition of high feed restriction, which might be attributed to less intensity of fat mobilisation under negative energy balance. The mechanism underlying resistance to such feed restriction was presumably through action of somatostain receptor 2 and was potentially mediated by inhibitory effects of somatostatin on growth hormone release but not basal growth hormone secretion.

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Evaluation of Hepatotoxicity with Treatment Doses of Flucytosine and Amphotericin B for Invasive Fungal Infections

BioMed Research International ◽

10.1155/2016/5398730 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 7

Author(s):

Alexandra Folk ◽

Coralia Cotoraci ◽

Cornel Balta ◽

Maria Suciu ◽

Hildegard Herman ◽

...

Keyword(s):

Amphotericin B ◽

Target Genes ◽

Fungal Infections ◽

Combined Therapy ◽

Hepatic Tissue ◽

Dependent Manner ◽

Liver Injuries ◽

Dose Dependent Increase ◽

Dose Dependent ◽

Different Doses

Invasive fungal infection is a well-known cause of morbidity and mortality in immunocompromised patients. In this study we aimed to evaluate the hepatotoxicity induced by combined therapy of flucytosine and amphotericin B, at three different doses administered to mice for 14 days: 50 mg/kg flucytosine and 300 μg/kg amphotericin B; 100 mg/kg flucytosine and 600 μg/kg amphotericin B; 150 mg/kg flucytosine and 900 μg/kg amphotericin B. Liver injuries were evaluated by analysis of optic and electron microscopy samples, changes in TNF-α, IL-6, and NF-κB inflammation markers levels of expression, and evaluation of mRNA profiles. Histological and ultrastructural analysis revealed an increase in parenchymal and portal inflammation in mice and Kupffer cells activation. Combined antifungal treatment stimulated activation of an inflammatory pathway, demonstrated by a significant dose-dependent increase of TNF-αand IL-6 immunoreactivity, together with mRNA upregulation. Also, NF-κB was activated, as suggested by the high levels found in hepatic tissue and upregulation of target genes. Our results suggest that antifungal combined therapy exerts a synergistic inflammatory activation in a dose-dependent manner, through NF-κB pathway, which promotes an inflammatory cascade during inflammation. The use of combined antifungal therapy needs to be dose limiting due to the associated risk of liver injury, especially for those patients with hepatic dysfunction.

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PSXIII-37 Alteration of mRNA abundance of the oxidizing factors-related genes during the transition period in dromedary camel

Journal of Animal Science ◽

10.1093/jas/skz258.730 ◽

2019 ◽

Vol 97 (Supplement_3) ◽

pp. 366-366

Author(s):

Mousa Zarrin ◽

Rachael Christensen ◽

S Kazem DoostMohammadi ◽

Ahmadali Ahmadpour ◽

Amir Ahmadpour

Keyword(s):

Repeated Measures ◽

Transition Period ◽

Thioredoxin Reductase ◽

Mrna Abundance ◽

Dromedary Camel ◽

Free Access ◽

Defense System ◽

Important Species ◽

Expression Of Genes ◽

Access To Water

Abstract Livestock near and during parturition have a complex defense system against environmental and physiological stresses. Little knowledge exists for some livestock species, such as camels, during this time. However, camels are an important species in some areas of the world. This study aimed to investigate the changes in the expression of genes responsible for the regeneration of hepatic oxidizing factors. Ten multiparous (2.38 ± 0.56; mean ± SEM parity) pregnant camels weighing 527.94 ± 73.46 kg BW were studied. Camels pastured daily, kept in individual stalls nightly with a partial mixed ration and free access to water while in stalls. Hepatic biopsies were taken days 60, 45, 30, and 15 antepartum (AP) and days 3, 15, 30, 45, and 60 postpartum (PP). The mRNA abundance of glutathione reductase (GSR1), thioredoxin reductase (TrxR1), and sulfiredoxin (Srx1) were determined using the qPCR technique. Significances were determined using the general linear model with repeated measures of IBM SPSS statistics software v. 21.0 and are presented as means ± SEM (Figure 1). Means differences were determined using LSD test and considered significant if P values < 0.05. Compared to d 60AP, mRNA abundance of TrxR1 and Srx1 reached their peak at d 3PP (P ≤ 0.03). Although TrxR1 decreased slightly by d 15 and 30PP compared to d 3PP (P = 0.04), it was higher compared to all AP time-points (P ≤ 0.05). mRNA abundance of Srx1 decreased at d 30PP compared to d 3PP (P = 0.05). In contrast, the frequency of the GSR1 mRNA was static until d 30PP, reduced slightly (P ≤ 0.05) then was unchanged to the end of the study period. These results show that genes responsible for hepatic oxidizing factors could be considered immunoregulatory factors for orchestrating cytoprotective systems against oxidative stress.

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Metabolic Stress in the Transition Period of Dairy Cows: Focusing on the Prepartum Period

Animals ◽

10.3390/ani10081419 ◽

2020 ◽

Vol 10 (8) ◽

pp. 1419

Author(s):

Osvaldo Bogado Pascottini ◽

Jo L. M. R. Leroy ◽

Geert Opsomer

Keyword(s):

Infectious Disease ◽

Dairy Cows ◽

Systemic Inflammation ◽

Postpartum Period ◽

Transition Period ◽

Metabolic Stress ◽

Negative Energy ◽

Spontaneous Reduction ◽

Fat Mobilization ◽

Transition Dairy Cows

All modern, high-yielding dairy cows experience a certain degree of reduced insulin sensitivity, negative energy balance, and systemic inflammation during the transition period. Maladaptation to these changes may result in excessive fat mobilization, dysregulation of inflammation, immunosuppression, and, ultimately, metabolic or infectious disease in the postpartum period. Up to half of the clinical diseases in the lifespan of high-yielding dairy cows occur within 3 weeks of calving. Thus, the vast majority of prospective studies on transition dairy cows are focused on the postpartum period. However, predisposition to clinical disease and key (patho)physiological events such as a spontaneous reduction in feed intake, insulin resistance, fat mobilization, and systemic inflammation already occur in the prepartum period. This review focuses on metabolic, adaptive events occurring from drying off until calving in high-yielding cows and discusses determinants that may trigger (mal)adaptation to these events in the late prepartum period.

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Relationship between expression pattern of vitamin D receptor, 1 alpha-hydroxylase enzyme, and chemokine RANTES genes and selected serum parameters during transition period in Holstein dairy cows

Veterinary Record Open ◽

10.1136/vetreco-2019-000339 ◽

2020 ◽

Vol 7 (1) ◽

pp. e000339

Author(s):

Hala A R Saed ◽

Hussam M M Ibrahim ◽

Sabry A El-Khodery ◽

Mohamed A Youssef

Keyword(s):

Gene Expression ◽

Vitamin D ◽

Dairy Cows ◽

Transition Period ◽

Post Partum ◽

Serum Levels ◽

Vdr Gene ◽

Genetic Expression ◽

Enzyme Gene ◽

Holstein Dairy Cows

ObjectivesThe objective of the present study was to evaluate the pattern of genetic expression of vitamin D receptor (VDR), 1 alpha-hydroxylase (1α-OHase) enzyme and chemokine regulated on activation normal T-cell expressed and secreted (RANTES) in peripheral blood of Holstein dairy cows during transition period.MethodsBlood samples were collected from 16 Holstein dairy cows at 3 weeks prior expected date of delivery (EDD), at the day of parturition, and 3 weeks post-partum for assessment of expression profile of studied genes using real-time PCR and measurement of glucose, ionized calcium (Ca), parathyroid hormone (PTH), inorganic phosphorous (P), sodium (Na), potassium (K), chloride (Cl), and magnesium (Mg) levels.ResultsCompared with 3 weeks prior EDD, VDR gene expression decreased significantly at the day of parturition then increased significantly at 3 weeks post-partum. The genetic expression of 1α-OHase enzyme as well as PTH, K, Na and Cl levels increased significantly at the day of parturition. The Ca level decreased significantly at the day of parturition then increased significantly at 3 weeks post-partum. The P level increased significantly at the day of parturition then decreased significantly at 3 weeks post-partum. Glucose level decreased significantly at the day of parturition and at 3 weeks post-partum. RANTES gene expression showed non-significant changes among the three different time points. The expression of VDR gene had a negative correlation with the expression of 1α-OHase enzyme gene, and serum levels of glucose, PTH, P and K, but had a positive correlation with the serum Ca level. The expression of 1α-OHase enzyme gene had a positive correlation with serum levels of PTH, P and K, but had a negative correlation with the serum Ca level.ConclusionsResults of the current study indicate the importance of monitoring the genetic expression of VDR and 1α-OHase enzyme as indicators of metabolic changes during transition period, suggesting that they are candidate genes to judge the health status of dairy cows during such period.

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Effect of feed restriction and subsequent re-alimentation on hormones and genes of the somatotropic axis in cattle

Physiological Genomics ◽

10.1152/physiolgenomics.00134.2014 ◽

2015 ◽

Vol 47 (7) ◽

pp. 264-273 ◽

Cited By ~ 4

Author(s):

Kate Keogh ◽

Sinéad M. Waters ◽

Alan K. Kelly ◽

Alastair R. G. Wylie ◽

David A. Kenny

Keyword(s):

Growth Hormone ◽

Compensatory Growth ◽

Hepatic Tissue ◽

Feed Restriction ◽

Lower Growth ◽

Somatotropic Axis ◽

Hepatic Expression ◽

Period 2 ◽

Lower Growth Rate ◽

Ad Libitum

The objective of this study was to characterize the effect of feed restriction and compensatory growth during re-alimentation on the functionality of the somatotropic axis. We blocked 60 bulls into one of two groups: 1) restricted feed allowance for 125 days ( period 1) (RES, n = 30) followed by ad libitum feeding for 55 days ( period 2) or 2) ad libitum access to feed throughout (ADLIB, n = 30). A growth hormone releasing hormone (GHRH) challenge was performed during each period. At the end of each period, 15 animals from each treatment were slaughtered and hepatic tissue collected. Hepatic expression of 13 genes of the somatotropic axis was measured by qRT-PCR. RES displayed a lower growth rate during period 1 (0.6 vs. 1.9 kg/day; P < 0.001), subsequently gaining more than ADLIB animals during period 2 (2.5 vs. 1.4 kg/day; P < 0.001). Growth hormone response to GHRH was not different between treatments at either time-point ( P > 0.05); however, resultant plasma IGF-1 was lower in period 1 and greater in period 2 in RES animals ( P < 0.05). Expression of IGFBP2 was higher ( P < 0.01) and IGF1 ( P < 0.001) and GHRIA ( P < 0.05) lower in RES compared with ADLIB during period 1, with no difference evident in period 2 ( P > 0.05). Collectively, the results of this study are consistent with uncoupling of the somatotropic axis following feed restriction. However, there is no evidence from this study that the somatotropic axis per se is a significant contributor to compensatory growth.

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