scholarly journals Treatment with PPARαAgonist Clofibrate Inhibits the Transcription and Activation of SREBPs and Reduces Triglyceride and Cholesterol Levels in Liver of Broiler Chickens

PPAR Research ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Lijun Zhang ◽  
Chunyan Li ◽  
Fang Wang ◽  
Shenghua Zhou ◽  
Mingjun Shangguan ◽  
...  

PPARαagonist clofibrate reduces cholesterol and fatty acid concentrations in rodent liver by an inhibition of SREBP-dependent gene expression. In present study we investigated the regulation mechanisms of the triglyceride- and cholesterol-lowering effect of the PPARαagonist clofibrate in broiler chickens. We observed that PPARαagonist clofibrate decreases the mRNA and protein levels of LXRαand the mRNA and both precursor and nuclear protein levels of SREBP1 and SREBP2 as well as the mRNA levels of the SREBP1 (FASNandGPAM) and SREBP2 (HMGCRandLDLR) target genes in the liver of treated broiler chickens compared to control group, whereas the mRNA level ofINSIG2, which inhibits SREBP activation, was increased in the liver of treated broiler chickens compared to control group. Taken together, the effects of PPARαagonist clofibrate on lipid metabolism in liver of broiler chickens involve inhibiting transcription and activation of SREBPs and SREBP-dependent lipogenic and cholesterologenic gene expression, thereby resulting in a reduction of the triglyceride and cholesterol levels in liver of broiler chickens.

2019 ◽  
Vol 64 (No. 2) ◽  
pp. 89-97
Author(s):  
A. Kubešová ◽  
K. Šťastný ◽  
M. Faldyna ◽  
Z. Sládek ◽  
I. Steinhauserová ◽  
...  

This study aimed to obtain a comprehensive look at the influence of castration on mRNA expression of the genes CYP2E1, CYP1A2, CYP2A19, HSD3B, SULT2A1 and SULT1A1 and their correlation with boar taint compounds (androstenone, skatole and indole) and Improvac-specific antibodies in a Czech commercial hybrid (Large White × Landrace (sow) × Duroc (boar)). Pigs were divided into groups of entire male pigs (NC), pigs castrated surgically (SC), pigs immunologically castrated and slaughtered 8 weeks (IM8) or 15 weeks (IM15) after the second dose of Improvac, and gilts (GI). Hepatic mRNA expression, measured by quantitative real-time polymerase chain reaction, differed significantly between the control group (entire male pigs) and all groups of interest for CYP2E1, CYP1A2 and CYP2A19. The mRNA level of the HSD3B gene differed significantly between the control group and the IM8, IM15 and GI groups. SULT1A1 gene expression was significantly different between the control group and the SC, IM8 and GI. In the case of SULT2A1, a significant difference was observed only between the control group and IM8 pigs. For all genes and treatment groups described above, expression was increased relative to the control. Significant differences for Improvac-specific antibodies between IM8 and IM15 groups were observed, indicating decrease of antibodies over time. Moreover, negative correlations between androstenone and mRNA levels of CYP2A19, CYP2E1 and SULT1A1 suggest that gene expression is suppressed.


1995 ◽  
Vol 269 (6) ◽  
pp. H1865-H1873 ◽  
Author(s):  
R. Kacimi ◽  
J. M. Moalic ◽  
A. Aldashev ◽  
D. E. Vatner ◽  
J. P. Richalet ◽  
...  

Chronic hypoxia impairs adrenergic responsiveness. A modulation of Gs and/or G1 protein alpha-subunits may be associated with the downregulation of the beta-adrenergic receptors previously found in chronic hypoxia. G protein gene expression and protein level and function in rat hearts exposed to a 30-day hypobaric chronic hypoxia were compared with control rat hearts. No change was observed in G alpha s mRNA levels in either right or left ventricles. In right ventricles, mRNA levels of G alpha i-2 increased by 40% (P < 0.05), but not in left ventricles. In both left and right ventricles, chronic hypoxia did not modify G alpha i-2 and G alpha s protein amounts, but significantly decreased functional activity of G alpha s. In conclusion, gene expression, protein levels of G alpha s and G alpha i-2, and activity of G alpha s do not change in parallel fashion with chronic hypoxia. In chronic hypoxic right ventricles, although the mRNA level of G alpha i-2 is increased, the protein level is unchanged. One potential mechanism of desensitization to catecholamines in chronic hypoxia appears to involve a decreased functional activity of G alpha s in spite of normal mRNA and protein levels


2021 ◽  
Author(s):  
Shamseddin Ahmadi ◽  
Shiva Mohammadi Talvar ◽  
Kayvan Masoudi ◽  
Mohammad Zobeiri

Abstract We aim to examine anxiety-like behaviors and expression of specific genes complicated in neuroinflammation in the prefrontal cortex (PFC) after repeated use of morphine. A group of male Wistar rats received injections of morphine (10 mg/kg) twice a day for eight days while a control group received saline (1 ml/kg) instead of morphine. On days 1 and 8, anxiety-like behaviors were evaluated using a light/dark box test. On day 8, opioid dependence was confirmed by measuring the behavioral expression of morphine withdrawal precipitated with naloxone. Expression of neuroinflammation genes were also evaluated at mRNA levels in the PFC on day 8. The results revealed that morphine induced anxiolytic-like effects on day 1, which significantly decreased after the repeated injection of the drug on day 8. The results also revealed that repeated morphine injection significantly increased the mRNA level of Il1, Tnfα, and Il6 but decreased Il1r and Tnfr while increased Il6r in the PFC. The gene expression results also revealed a significant decrease in Tlr1 but not in Tlr4 in the PFC of morphine-dependent rats. Although Erk1 expression had no significant alteration but p38 increased and Jnk3 decreased significantly in the PFC in morphine-dependent rats. Creb and Nfkb significantly increased but Fos expression decreased. Let-7c, mir-133b, and mir-365 also significantly increased in the PFC in morphine-dependent rats. We conclude that the alteration in neuroinflammatory pathways at gene expression level in the PFC may party underlie neuroadaptive changes leading to the decrease in anxiolytic effect of morphine in dependent rats.


2019 ◽  
Vol 97 (8) ◽  
pp. 3180-3192 ◽  
Author(s):  
Yong Zhang ◽  
Bing Yu ◽  
Jie Yu ◽  
Ping Zheng ◽  
Zhiqing Huang ◽  
...  

Abstract The present study aimed to investigate the influence of dietary butyrate supplementation on muscle fiber-type composition and mitochondrial biogenesis of finishing pigs, and the underlying mechanisms. Thirty-two LY (Landrace × Yorkshire) growing pigs with BW of 64.9 ± 5.7 kg were randomly allotted to either control (basal diet) or butyrate diets (0.3% butyrate sodium). Compared with the control group, diet supplemented with butyrate tended to increase average daily gain (P < 0.10). Pigs fed butyrate diet had higher intramuscular fat content, marbling score and pH24 h, and lower shear force and L*24 h in longissimus thoracis (LT) muscle than that fed control diet (P < 0.05). Interestingly, supplemented with butyrate increased (P < 0.05) the mRNA level of myosin heavy chain I (MyHC-I) and the percentage of slow-fibers, and decreased (P < 0.05) the mRNA level of MyHC-IIb in LT muscle. Meanwhile, pigs in butyrate group had an increase in mitochondrial DNA (mtDNA) copy number and the mRNA levels of mtDNA-encoded genes (P < 0.05). Moreover, feeding butyrate diet increased PGC-1α (PPAR γ coactivator 1α) level, decreased miR-133a-3p level and increased its target gene level (TEAD1, TEA domain transcription factor 1), increased miR-208b and miR-499-5p levels and decreased their target genes levels (Sp3 and Sox6, specificity protein 3 and SRY-box containing gene 6; P < 0.05) in the LT muscle. Collectively, these findings suggested that butyrate promoted slow-twitch myofiber formation and mitochondrial biogenesis, and the molecular mechanism may be via upgrading specific microRNAs and PGC-1α expression, finally improving meat quality.


2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Junco S Warren ◽  
Amira Sabry ◽  
Keiko Cawley ◽  
Aman Makaju ◽  
Marta W Szulik ◽  
...  

Smyd1, a muscle-specific histone methyltransferase, has been implicated in global metabolic remodeling in cardiac hypertrophy and failure. We previously showed that cardiac-specific ablation of Smyd1 in mice led to metabolic perturbations prior to overt cardiac dysfunction, suggesting that Smyd1 positively regulates cardiac metabolism. However, the role of Smyd1 in adaptive response to nutritional stress (NS) in cardiomyocytes is largely unknown. Here, we found that glucose deprivation-induced NS led to upregulation of Smyd1 in cultured rat neonatal ventricular myocytes (NRVMs) (FC=1.87, p<0.05), which was associated with the increased mRNA level of PGC-1α, a key regulator of mitochondrial energetics (FC=2.71, p<0.05). Strikingly, siRNA-mediated knockdown of Smyd1 (Smyd1-KD) in NRVM prior to glucose starvation led to extensive cell death not observed in control NRVMs (scrambled siRNA), suggesting that Smyd1 is required for cell survival in NS. To elucidate the mechanism how Smyd1 is involved in adaptive response to NS, we performed unbiased proteomic and metabolomic screening of Smyd1-KD NRVMs. Bioinformatic analysis of proteins and metabolites that were differentially expressed in Smyd1-KD NRVM revealed that oxidative phosphorylation was the most perturbed metabolic pathway in Smyd1-KD NRVMs, concomitant with a reduction in mitochondrial substrates (BCAAs; pyruvate; lactate, all p<0.05). Gene expression analyses using RT-PCR and RNA-seq in Smyd1-KD NRVMs further identified PGC-1α and Perm1 (the muscle-specific PGC-1α and ESRR induced regulator) as potential downstream targets of Smyd1 in regulation of cardiac energetics (FC=-1.92 and -1.66, respectively, both p<0.05). Consistent with downregulation of Perm1, the known Perm1-target genes (Tfb1m; Ctp1b; Glut4; Myl2) were all downregulated at the mRNA levels in Smyd1-KD NRVMs (p<0.05). Lastly, Smyd1-KD NRVMs exhibited accelerated loss of mitochondrial membrane potential during hypoxia, revealing an increased vulnerability to metabolic stress. Taken together, these results show that Smyd1 is an essential regulator of adaptive response and cell survival during metabolic insults, presumably through regulating PGC-1α/Perm1 gene expression.


2003 ◽  
Vol 30 (2) ◽  
pp. 253-262 ◽  
Author(s):  
M Imae ◽  
Z Fu ◽  
A Yoshida ◽  
T Noguchi ◽  
H Kato

Transcription factors of the FoxO family in mammals are orthologues of the Caenorhabditis elegans forkhead factor DAF-16, which has been characterized as a target of insulin-like signalling. Three members of this family have been identified in rodents: FoxO1, FoxO3 and FoxO4, originally termed FKHR, FKHRL1 and AFX respectively. A number of in vitro studies have revealed that FoxOs are regulated through phosphorylation in response to insulin and related growth factors, resulting in their nuclear exclusion and inactivation. To clarify the mechanisms involved in the regulation of these factors in vivo, we investigated in the present study whether or not, and if so how, their mRNA levels in rat liver respond to the stimuli of several nutritional and hormonal factors. Imposed fasting for 48 h significantly elevated mRNA levels of FoxO1 (1.5-fold), FoxO3 (1.4-fold), and FoxO4 (1.6-fold). Refeeding for 3 h recovered the induced mRNA levels of FoxO1 and FoxO3 to the control levels, but did not affect that of FoxO4. FoxO1 and FoxO4 mRNA levels were proved to be highly reflective of their protein levels measured by Western immunoblotting. Of the three FoxO genes, FoxO4 only showed altered levels of mRNA (a 1.5-fold increase) in response to a protein-free diet. Streptozotocin-induced diabetes for 28 days decreased hepatic mRNA levels of FoxO1 and FoxO3 and increased the level of FoxO4 mRNA, but short-term (7 days) diabetes had fewer effects on the expression of these genes. Insulin replacement partially restored the FoxO1 and FoxO4 mRNA levels, but had no effect on the FoxO3 mRNA level. Daily administration for 1 week of dexamethasone, a synthetic glucocorticoid, increased the mRNA levels of FoxO1 (1.8-fold) and FoxO3 (2.4-fold). These results show that the FoxO genes respond differently to nutritional and hormonal factors, suggesting a new mechanism for the regulation of FoxO-dependent gene expression by these factors. Moreover, changes of FoxO1 and FoxO4 in the nucleus in response to fasting also suggest that the regulation of nucleus/cytoplasm translocation actually functions in vivo.


Pathobiology ◽  
2021 ◽  
pp. 1-12
Author(s):  
Ying Xie ◽  
Yuanyuan Ruan ◽  
Huimei Zou ◽  
Yixin Wang ◽  
Xin Wu ◽  
...  

<b><i>Objective:</i></b> The goal of the present study was to determine the expression of yes-associated protein 1 (YAP1) in renal tissues of mice with lupus nephritis (LN) and elucidate its role in the progression of renal fibrosis. <b><i>Methods:</i></b> C57BL/6 mice and MRL/lpr mice were selected for experimental comparison. Mouse kidney tissues were removed and sectioned for hematoxylin and eosin staining, Masson’s trichome staining, Sirius staining, and immunohistochemistry. The mRNA and protein levels of YAP1 in mouse kidney tissues were detected, and the correlation between YAP1 and fibronectin (FN) mRNA levels was analyzed. Mouse renal epithelial cells were used for in vitro experiments. After transfection and stimulation, the cells were divided into 4 groups, namely the C57BL/6 serum group (group 1), the MRL/lpr serum group (group 2), the MRL/lpr serum + siRNA-negative control group (group 3), and the MRL/lpr serum + siRNA-YAP1 group (group 4). Epithelial-mesenchymal transition (EMT) markers in each group were detected by Western blotting and immunofluorescence staining. Serum creatinine, blood urea nitrogen, and urinary protein levels were detected and assessed for their correlation with YAP1 mRNA levels by Spearman’s analysis. <b><i>Results:</i></b> Compared to C57BL/6 mice, MRL/lpr mice exhibited obvious changes in fibrosis in renal tissues. In addition, YAP1 expression was significantly higher in the renal tissues of MRL/lpr mice than in those of C57BL/6 mice, and YAP1 mRNA levels were positively correlated with those of FN. YAP1 silencing in lupus serum-stimulated cells could effectively relieve serum-induced EMT. Finally, we observed that YAP1 mRNA levels in mouse kidney tissue were significantly and positively correlated with the degree of renal function injury. <b><i>Conclusion:</i></b> YAP1 expression in the kidney tissues of LN mice was higher than that observed in normal mice, indicating that YAP1 may play an important role in the occurrence and development of LN.


2008 ◽  
Vol 100 (4) ◽  
pp. 2015-2025 ◽  
Author(s):  
Julie E. Miller ◽  
Elizabeth Spiteri ◽  
Michael C. Condro ◽  
Ryan T. Dosumu-Johnson ◽  
Daniel H. Geschwind ◽  
...  

Cognitive and motor deficits associated with language and speech are seen in humans harboring FOXP2 mutations. The neural bases for FOXP2 mutation-related deficits are thought to reside in structural abnormalities distributed across systems important for language and motor learning including the cerebral cortex, basal ganglia, and cerebellum. In these brain regions, our prior research showed that FoxP2 mRNA expression patterns are strikingly similar between developing humans and songbirds. Within the songbird brain, this pattern persists throughout life and includes the striatal subregion, Area X, that is dedicated to song development and maintenance. The persistent mRNA expression suggests a role for FoxP2 that extends beyond the formation of vocal learning circuits to their ongoing use. Because FoxP2 is a transcription factor, a role in shaping circuits likely depends on FoxP2 protein levels which might not always parallel mRNA levels. Indeed our current study shows that FoxP2 protein, like its mRNA, is acutely downregulated in mature Area X when adult males sing with some differences. Total corticosterone levels associated with the different behavioral contexts did not vary, indicating that differences in FoxP2 levels are not likely attributable to stress. Our data, together with recent reports on FoxP2's target genes, suggest that lowered FoxP2 levels may allow for expression of genes important for circuit modification and thus vocal variability.


2021 ◽  
Vol 22 (3) ◽  
pp. 1478
Author(s):  
Jiayin Lu ◽  
Yaoxing Chen ◽  
Zixu Wang ◽  
Jing Cao ◽  
Yulan Dong

Restraint stress causes various maternal diseases during pregnancy. β2-Adrenergic receptor (β2-AR) and Forkhead transcription factor class O 1 (FOXO1) are critical factors not only in stress, but also in reproduction. However, the role of FOXO1 in restraint stress, causing changes in the β2-AR pathway in pregnant mice, has been unclear. The aim of this research was to investigate the β2-AR pathway of restraint stress and its impact on the oxidative stress of the maternal uterus. In the study, maternal mice were treated with restraint stress by being restrained in a transparent and ventilated device before sacrifice on Pregnancy Day 5 (P5), Pregnancy Day 10 (P10), Pregnancy Day 15 (P15), and Pregnancy Day 20 (P20) as well as on Non-Pregnancy Day 5 (NP5). Restraint stress augmented blood corticosterone (CORT), norepinephrine (NE), and blood glucose levels, while oestradiol (E2) levels decreased. Moreover, restraint stress increased the mRNA levels of the FOXO family, β2-AR, and even the protein levels of FOXO1 and β2-AR in the uterus and ovaries. Furthermore, restraint stress increased uterine oxidative stress level. In vitro, the protein levels of FOXO1 were also obviously increased when β2-AR was activated in endometrial stromal cells (ESCs). In addition, phosphorylated-nuclear factor kappa-B p65 (p-NF-κB p65) and its target genes decreased significantly when FOXO1 was inhibited. Overall, it can be said that the β2-AR/FOXO1/p-NF-κB p65 pathway was activated when pregnant mice were under restraint stress. This study provides a scientific basis for the origin of psychological stress in pregnant women.


2012 ◽  
Vol 120 (02) ◽  
pp. 84-88 ◽  
Author(s):  
S. Chen ◽  
X. Zhuang ◽  
Y. Liu ◽  
A. Sun ◽  
C. Chen

AbstractLipin1, a lately indentified adipokine, may link obesity with insulin resistance and diabetes. The present study aimed to investigate the changes and significance of lipin1 expression and lipin1-AMPK signaling in diet-induced hepatic insulin resistance.24 4-week-old Male Wistar rats were randomly divided into 2 groups: (1) control group (CO), (2) high-fat diet group (HF). Insulin sensitivity was evaluated by hyperinsulinemic-euglycemic clamp technique. The mRNA levels of α1 and α2 subunit of AMPKα as well as Lipin1 were measured using Real-time RT-PCR. The activities of AMPKα and Akt were evaluated by detection of p-AMPKα (Thr-172) and p-Akt (ser473) by Western blot.After treatment of 4 months, HF group showed significantly increased levels of body weight, fasting plasma glucose and insulin levels; Plasma and liver total cholesterol (TC), triglycerides (TG) levels were also markedly elevated; Lipin1 expression at both mRNA and protein levels were significantly deceased. Compared with CO group, the mRNA and protein levels of AMPKα1 and AMPKα2 were not changed, whereas the p-AMPK (Thr-172) and p-AKT (ser473) levels in liver were significantly decreased in HF group.These findings indicated that the decrease in lipin1 expression and AMPKα activation may contribute to hepatic insulin resistance in diet-induced obese rats.


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