scholarly journals Analysis of Differentially Expressed Genes in Gastrocnemius Muscle between DGAT1 Transgenic Mice and Wild-Type Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Fei Ying ◽  
Hao Gu ◽  
Yuanzhu Xiong ◽  
Bo Zuo

Adipose tissue was the major energy deposition site of the mammals and provided the energy for the body and released the external pressure to the internal organs. In animal production, fat deposition in muscle can affect the meat quality, especially the intramuscular fat (IMF) content. Diacylglycerol acyltransferase-1 (DGAT1) was the key enzyme to control the synthesis of the triacylglycerol in adipose tissue. In order to better understand the regulation mechanism of the DGAT1 in the intramuscular fat deposition, the global gene expression profiling was performed in gastrocnemius muscle between DGAT1 transgenic mice and wild-type mice by microarray. 281 differentially expressed transcripts were identified with at least 1.5-fold change and thepvalue < 0.05. 169 transcripts were upregulated and 112 transcripts were downregulated. Ten genes (SREBF1, DUSP1, PLAGL1, FKBP5, ZBTB16, PPP1R3C, CDC14A, GLUL, PDK4, and UCP3) were selected to validate the reliability of the chip’s results by the real-time PCR. The finding of RT-PCR was consistent with the gene chip. Seventeen signal pathways were analyzed using KEGG pathway database and the pathways concentrated mainly on the G-protein coupled receptor protein signaling pathway, signal transduction, oxidation-reduction reaction, olfactory receptor activity, protein binding, and zinc ion binding. This study implied a function role of DGAT1 in the synthesis of TAG, insulin resistance, and IMF deposition.

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246279
Author(s):  
Jilong Han ◽  
Tingting Guo ◽  
Yaojing Yue ◽  
Zengkui Lu ◽  
Jianbin Liu ◽  
...  

Tail adipose as one of the important functional tissues can enhance hazardous environments tolerance for sheep. The objective of this study was to gain insight into the underlying development mechanisms of this trait. A quantitative analysis of protein abundance in ovine tail/rump adipose tissue was performed between Chinese local fat- (Kazakh, Hu and Lanzhou) and thin-tailed (Alpine Merino, Tibetan) sheep in the present study by using lable-free approach. Results showed that 3400 proteins were identified in the five breeds, and 804 were differentially expressed proteins, including 638 up regulated proteins and 83 down regulated proteins in the tail adipose tissues between fat- and thin-tailed sheep, and 8 clusters were distinguished for all the DEPs’ expression patterns. The differentially expressed proteins are mainly associated with metabolism pathways and peroxisome proliferator activated receptor signaling pathway. Furthermore, the proteomics results were validated by quantitative real-time PCR and Western Blot. Our research has also suggested that the up-regulated proteins ACSL1, HSD17β4, FABP4 in the tail adipose tissue might contribute to tail fat deposition by facilitating the proliferation of adipocytes and fat accumulation in tail/rump of sheep. Particularly, FABP4 highly expressed in the fat-tail will play an important role for tail fat deposition. Our study might provide a novel view to understanding fat accumulation in special parts of the body in sheep and other animals.


2018 ◽  
Vol 50 (6) ◽  
pp. 2406-2422 ◽  
Author(s):  
Wanlong Huang ◽  
Xiuxiu Zhang ◽  
Ai Li ◽  
Lingli Xie ◽  
Xiangyang Miao

Background/Aims: Long non-coding RNAs (lncRNAs) can regulate adipogenesis and lipid accumulation. Intramuscular fat deposition appears to vary in different pig breeds, and the regulation mechanism has not yet been fully elucidated at molecular level. Moreover, little is known about the function and profile of lncRNAs in intramuscular fat deposition and metabolism in pig. The aim of this study was thus to explore the regulatory functions of lncRNAs in intramuscular fat deposition. Methods: In this study, Laiwu (LW) pig and Large White (LY) pig with significant difference in fat deposition were selected for use. RNA-seq technology and bioinformatics methods were used to comparatively analyze the gene expression profiles of intramuscular fat between LW and LY pigs to identify key mRNAs and lncRNAs associated with lipid metabolism and adipogenesis. Real-time fluorescence-based quantitative PCR was applied to verify the expression level of the differentially expressed mRNAs and lncRNAs. Results: A total of 513 mRNAs and 55 lncRNAs were differentially expressed between two pig breeds. By co-expression network construction as well as cis- and trans-regulated target gene analysis, 31 key lncRNAs were identified. Gene Ontology and KEGG pathway analyses revealed that differentially expressed genes and lncRNAs were mainly involved in the biological processes and pathways related to adipogenesis and lipid metabolism. Conclusion: XLOC_046142, XLOC_004398 and XLOC_015408 may target MAPKAPK2, NR1D2 and AKR1C4, respectively, and play critical regulatory roles in intramuscular adipogenesis and lipid accumulation in pig. XLOC_064871 and XLOC_011001 may play a role in lipid metabolism-related disease via regulating TRIB3 and BRCA1. This study provides a valuable resource for lncRNA study and improves our understanding of the biological roles of lipid metabolism- related genes and molecular mechanism of intramuscular fat metabolism and deposition.


2021 ◽  
Author(s):  
Wai W Cheung ◽  
Ronghao Zheng ◽  
Sheng Hao ◽  
Zhen Wang ◽  
Alex Gonzalez ◽  
...  

Abstract Cytokines such as IL-6, TNF-α and IL-1β trigger inflammatory cascades which may play a role in the pathogenesis of chronic kidney disease (CKD)-associated cachexia. CKD was induced by 5/6 nephrectomy in mice. We studied energy homeostasis in Il1β −/−/CKD, Il6−/−/CKD and Tnfα −/−/CKD mice and compared with wild type (WT)/CKD controls. Parameters of cachexia phenotype were completely normalized in Il1β −/−/CKD mice but were only partially rescued in Il6−/−/CKD and Tnfα −/−/CKD mice. We tested the effects of anakinra, an IL-1 receptor antagonist, on CKD-associated cachexia. WT/CKD mice were treated with anakinra (2.5 mg.kg.day, IP) or saline for 6 weeks and compared with WT/sham controls. Anakinra normalized food intake and weight gain, fat and lean mass content, metabolic rate and muscle function, and also attenuated molecular perturbations of energy homeostasis in adipose tissue and muscle in WT/CKD mice. Anakinra attenuated browning of white adipose tissue in WT/CKD mice. Moreover, anakinra normalized gastrocnemius weight and fiber size as well as attenuated muscle fat infiltration in WT/CKD mice. This was accompanied by correcting the increased muscle wasting signaling pathways while promoting the decreased myogenesis process in gastrocnemius of WT/CKD mice. We performed qPCR analysis for the top 20 differentially expressed muscle genes previously identified via RNAseq analysis in WT/CKD mice versus controls. Importantly, 17 differentially expressed muscle genes were attenuated in anakinra treated WT/CKD mice. In conclusion, IL-1 receptor antagonism may represent a novel targeted treatment for adipose tissue browning and muscle wasting in CKD.


Endocrinology ◽  
2012 ◽  
Vol 153 (4) ◽  
pp. 1706-1716 ◽  
Author(s):  
Fen Xu ◽  
David Burk ◽  
Zhanguo Gao ◽  
Jun Yin ◽  
Xia Zhang ◽  
...  

The histone deacetylase sirtuin 1 (SIRT1) inhibits adipocyte differentiation and suppresses inflammation by targeting the transcription factors peroxisome proliferator-activated receptor γ and nuclear factor κB. Although this suggests that adiposity and inflammation should be enhanced when SIRT1 activity is inactivated in the body, this hypothesis has not been tested in SIRT1 null (SIRT1−/−) mice. In this study, we addressed this issue by investigating the adipose tissue in SIRT1−/− mice. Compared with their wild-type littermates, SIRT1 null mice exhibited a significant reduction in body weight. In adipose tissue, the average size of adipocytes was smaller, the content of extracellular matrix was lower, adiponectin and leptin were expressed at 60% of normal level, and adipocyte differentiation was reduced. All of these changes were observed with a 50% reduction in capillary density that was determined using a three-dimensional imaging technique. Except for vascular endothelial growth factor, the expression of several angiogenic factors (Pdgf, Hgf, endothelin, apelin, and Tgf-β) was reduced by about 50%. Macrophage infiltration and inflammatory cytokine expression were 70% less in the adipose tissue of null mice and macrophage differentiation was significantly inhibited in SIRT1−/− mouse embryonic fibroblasts in vitro. In wild-type mice, macrophage deletion led to a reduction in vascular density. These data suggest that SIRT1 controls adipose tissue function through regulation of angiogenesis, whose deficiency is associated with macrophage malfunction in SIRT1−/− mice. The study supports the concept that inflammation regulates angiogenesis in the adipose tissue.


2020 ◽  
Author(s):  
Supanon Tunim ◽  
Yupin Phasuk ◽  
Samuel E. Aggrey ◽  
Monchai Duangjinda

Abstract Background: Crossbreeding using exotic breeds is usually employed to improve the growth characteristics of indigenous chickens. This mating not only provides growth but affect adversely to fat deposition as well. We studied the growth, abdominal, subcutaneous and intramuscular fat and mRNA expression of peroxisome proliferator-activated receptor (PPAR) α and PPARγ in adipose and muscle tissues of four chicken breeds [Chee breed (CH) (100% Thai native chicken), Kaimook e-san1 (KM1; 50% CH background), Kaimook e-san2 (KM2; 25% CH background), and broiler (BR)]. This study was aim to study role of PPARs on fat deposition in native crossbred chicken.Results: The BR chickens had higher abdominal fat than other breeds (P<0.05) and the KM2 had an abdominal fat percentage higher than KM1 and CH respectively (P<0.05). The intramuscular fat (IMF) of BR was greater than KM1 and CH (P<0.05). In adipose tissue, PPARα transcription expression was different among the chicken breeds. However, there were breed differences in PPARγ gene expression. Study of abdominal fat PPARγ gene expression showed the BR breed, KM1, and KM2 breed significantly greater (P<0.05) than CH. In 8 to 12 weeks of age, the result shows that the PPARγ expression of the CH breed is less than (P<0.05) KM2. The result of PPARs expression in muscle tissue was similar result in adipose tissue.Conclusion: Crossbreeding improved the growth of the Thai native breed, there was also a corresponding increase in carcass fatness. However, there appears to be a relationship between PPARγ expression and fat deposition traits. therefore, PPARγ activity plays a key role in lipid accumulation by up-regulation.


2020 ◽  
Author(s):  
Fuhui Han ◽  
Jing Li ◽  
Nan Liu ◽  
Ranran Zhao ◽  
Lirong Liu ◽  
...  

Abstract Background: Intramuscular fat (IMF) content has become one of the most important indicators for measuring meat quality, and its level is affected by various genes. Long non-coding RNAs (lncRNAs) are widely expressed non-coding RNAs that play an important regulatory role in a variety of biological processes; however, research on lncRNAs involved in sheep intramuscular fat deposition is still in its infancy. Aohan fine-wool sheep (AFWS), China's representative meat-hair, dual-purpose sheep breed, provides a great model for studying the role of lncRNAs in the regulation of intramuscular fat deposition. We identified lncRNAs by RNA sequencing in sheep longissimus dorsi muscle(LDM) samples at two ages: 2 months (Mth-2) and 12 months (Mth-12).Results: We identified a total of 26,247 genes and 6,935 predicted novel lncRNAs in LDM samples of sheep. Among these, 606 mRNAs and 408 lncRNAs were differentially expressed. We then compared the structural characteristics of lncRNAs and mRNAs. We obtained targeted genes of differentially expressed lncRNAs and performed an enrichment analysis using Gene Ontology(GO) and the Kyoto Encyclopedia of Genes and Genomes(KEGG). We found these targeted mRNAs were primarily enriched in lipid metabolism, lipid transport, regulation of primary metabolic processes and developmental pathways, such as alpha-linolenic acid metabolism, biosynthesis of unsaturated fatty acids, phosphonate and phosphinate metabolism and cell proliferation. Based on the results of this enrichment analysis, we obtained candidate lncRNAs that potentially regulate lipid deposition and constructed a lncRNA-mRNA co-expression network. We speculated that these lncRNAs have important regulatory roles in intramuscular fat deposition. We randomly selected five mRNAs and five lncRNAs to verify the accuracy of sequencing results by qRT-PCR.Conclusions: Our study provided a list of the lncRNAs and mRNAs related to intramuscular lipid deposition in sheep and lay the foundation for future research on regulatory mechanisms.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wai W. Cheung ◽  
Ronghao Zheng ◽  
Sheng Hao ◽  
Zhen Wang ◽  
Alex Gonzalez ◽  
...  

AbstractCytokines such as IL-6, TNF-α and IL-1β trigger inflammatory cascades which may play a role in the pathogenesis of chronic kidney disease (CKD)-associated cachexia. CKD was induced by 5/6 nephrectomy in mice. We studied energy homeostasis in Il1β−/−/CKD, Il6−/−/CKD and Tnfα−/−/CKD mice and compared with wild type (WT)/CKD controls. Parameters of cachexia phenotype were completely normalized in Il1β−/−/CKD mice but were only partially rescued in Il6−/−/CKD and Tnfα−/−/CKD mice. We tested the effects of anakinra, an IL-1 receptor antagonist, on CKD-associated cachexia. WT/CKD mice were treated with anakinra (2.5 mg/kg/day, IP) or saline for 6 weeks and compared with WT/Sham controls. Anakinra normalized food intake and weight gain, fat and lean mass content, metabolic rate and muscle function, and also attenuated molecular perturbations of energy homeostasis in adipose tissue and muscle in WT/CKD mice. Anakinra decreased serum and muscle expression of IL-6, TNF-α and IL-1β in WT/CKD mice. Anakinra attenuated browning of white adipose tissue in WT/CKD mice. Moreover, anakinra normalized gastrocnemius weight and fiber size as well as attenuated muscle fat infiltration in WT/CKD mice. This was accompanied by correcting the increased muscle wasting signaling pathways while promoting the decreased myogenesis process in gastrocnemius of WT/CKD mice. We performed qPCR analysis for the top 20 differentially expressed muscle genes previously identified via RNAseq analysis in WT/CKD mice versus controls. Importantly, 17 differentially expressed muscle genes were attenuated in anakinra treated WT/CKD mice. In conclusion, IL-1 receptor antagonism may represent a novel targeted treatment for adipose tissue browning and muscle wasting in CKD.


2019 ◽  
Vol 16 (1) ◽  
pp. 55-61
Author(s):  
Natalya B. Chabanova ◽  
Tatiana N. Vasilkova ◽  
Valentina A. Polyakova ◽  
Sergey I. Mataev

BACKGROUND: Currently, obesity is one of the most global problem in the world. Redundant accumulation of adipose tissue accompanied by metabolic disorders including high secretion of leptin may lead to an increased risk of gestational complications. AIMS: To assess the level of leptin in pregnant womens blood serum depending on their body weight and the character of content of adipose tissue in different terms of gestation. MATERIALS AND METHODS: We investigated 211 women with single pregnancies, which came in natural cycles and finished with urgent parturitions. All of them got anthropometric study, assessment of adipose tissues weight by bioimpedanceometry, character of fat deposition by ultrasound investigation of adipose tissue, determination of the level of whey leptin at 1014, 2428, 3638 weeks of pregnancy. RESULTS: Established, that the level of leptin increases in proportion to pregestational body mass index from the first trimester. Women with excess body mass and with obesity had higher concentrations of leptin all over gestation, than women with normal body mass (р0.001). The higher term of pregnancy was, the higher the level of whey leptin was in all groups, independently of character of fat deposition. In the end of third trimester, women with normal body mass had the largest value of absolute and relative increase of body mass and fatty mass, what accompanied by enlargement of the concentration of leptin more than in 3 times for the pregestational level. CONCLUSIONS: In this way, high content of leptin in pregnant womens (with excess body mass and obesity) blood serum in the first trimester is explained by redundant accumulation of the adipose tissue. The largest value of gestational increase of body mass and fat mass in group where women had normal initial weight is accompanied by the great increase of the level of leptin on the body weight unit and fat mass. These data indicate, that control and limitation of excessive weight gain while pregnancy can be a measure of prevention of the redundant leptins secretion and different gestational complications related with it.


2014 ◽  
Author(s):  
Robert A Ngala ◽  
Mohamed S Zaibi ◽  
Kenneth Langlands ◽  
Claire J Stocker ◽  
Jonathan RS Arch ◽  
...  

Kv1 channels are shaker-related potassium channels that influence insulin sensitivity. Kv1.3 -/- mice are protected from diet-induced insulin resistance and some studies suggest that Kv1.3 inhibitors provide similar protection. However, it is unclear whether blockade of Kv1.3 in adipocytes or skeletal muscle increases glucose uptake. There is no evidence that the related channel Kv1.5 has any influence on insulin sensitivity and its expression in adipose tissue has not been reported. PAP-1 is a selective inhibitor of Kv1.3, with 23-fold, 32-fold and 125-fold lower potencies as an inhibitor of Kv1.5, Kv1.1 and Kv1.2 respectively. Soleus muscles from wild-type and genetically obese ob/ob mice were incubated with 2-deoxy[1-14C]-glucose for 45 min and formation of 2-deoxy[1-14C]-glucose-6-phosphate was measured. White adipocytes were incubated with D-[U-14C]-glucose for 1h. TNFalpha and Il-6 secretion from white adipose tissue pieces were measured by enzyme-linked-immunoassay. In the absence of insulin, a high concentration (3 μM) of PAP-1 stimulated 2-deoxy[1-14C]-glucose uptake in soleus muscle of wild-type and obese mice by 30% and 40% respectively, and in adipocytes by 20% and 50% respectively. PAP-1 also stimulated glucose uptake by adipocytes at the lower concentration of 1 μM, but at 300 nM, which is still 150-fold higher than its EC50 value for inhibition of the Kv1.3 channel, it had no effect. In the presence of insulin, PAP-1 (3 μM) had a significant effect only in adipocytes from obese mice. PAP-1 (3 μM) reduced the secretion of TNFalpha by adipose tissue but had no effect on the secretion of IL-6. Expression of Kv1.1, Kv1.2, Kv1.3 and Kv1.5 was determined by RT-PCR. Kv1.3 and Kv1.5 mRNA were detected in liver, gastrocnemius muscle, soleus muscle and white adipose tissue from wild-type and ob/ob mice, except that Kv1.3 could not be detected in gastrocnemius muscle, nor Kv1.5 in liver, of wild-type mice. Expression of both genes was generally higher in liver and muscle of ob/ob mice compared to wild-type mice. Kv1.5 appeared to be expressed more highly than Kv1.3 in soleus muscle, adipose tissue and adipocytes of wild-type mice. Expression of Kv1.2 appeared to be similar to that of Kv1.3 in soleus muscle and adipose tissue, but Kv1.2 was undetectable in adipocytes. Kv1.1 could not be detected in soleus muscle, adipose tissue or adipocytes. We conclude that inhibition of Kv1 channels by PAP-1 stimulates glucose uptake by adipocytes and soleus muscle of wild-type and ob/ob mice, and reduces the secretion of TNFalpha by adipose tissue. However, these effects are more likely due to inhibition of Kv1.5 than to inhibition of Kv1.3 channels.


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