scholarly journals De Novo Reconstruction of Transcriptome Identified Long Non-Coding RNA Regulator of Aging-Related Brown Adipose Tissue Whitening in Rabbits

Biology ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1176
Author(s):  
Kun Du ◽  
Xue Bai ◽  
Li Yang ◽  
Yu Shi ◽  
Li Chen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
De Novo ◽  
Expression Patterns ◽  
Wnt Signaling Pathway ◽  
Guanosine Monophosphate ◽  
Brown Adipocyte ◽  
Signal Pathways ◽  
Peroxisome Proliferator ◽  
Adipose Tissues ◽  
Brown Adipose

Brown adipose tissues (BATs) convert to a “white-like” phenotype with age, which is also known as “aging-related BAT whitening (ARBW)”. Emerging evidence suggested that long non-coding RNAs (lncRNAs) were widely involved in adipose biology. Rabbit is an ideal model for studying the dynamics of ARBW. In this study, we performed histological analysis and strand-specific RNA-sequencing (ssRNA-seq) of rabbit interscapular adipose tissues (iATs). Our data indicated that the rabbit iATs underwent the ARBW from 0 days to 2 years and a total of 2281 novel lncRNAs were identified in the iATs. The classical rabbit BATs showed low lncRNA transcriptional complexity compared to white adipose tissues (WATs). A total of 631 differentially expressed lncRNAs (DELs) were identified in four stages. The signal pathways of purine metabolism, Wnt signaling pathway, peroxisome proliferator-activated receptor (PPAR) signaling pathway, cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase (cGMP-PKG) signaling pathway and lipid and atherosclerosis were significantly enriched by the DELs with unique expression patterns. A novel lncRNA that was highly expressed in the iATs of aged rabbits was validated to impair brown adipocyte differentiation in vitro. Our study provided a comprehensive catalog of lncRNAs involved in ARBW in rabbits, which facilitates a better understanding of adipose biology.

scholarly journals ASKA technology-based pull-down method reveals a suppressive effect of ASK1 on the inflammatory NOD-RIPK2 pathway in brown adipocytes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Saki Takayanagi ◽  
Kengo Watanabe ◽  
Takeshi Maruyama ◽  
Motoyuki Ogawa ◽  
Kazuhiro Morishita ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Biological Significance ◽  
Suppressive Effect ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
Adipose Tissues ◽  
Signaling Complex ◽  
Brown Adipose ◽  
Immune Pathway

AbstractRecent studies have shown that adipose tissue is an immunological organ. While inflammation in energy-storing white adipose tissues has been the focus of intense research, the regulatory mechanisms of inflammation in heat-producing brown adipose tissues remain largely unknown. We previously identified apoptosis signal-regulating kinase 1 (ASK1) as a critical regulator of brown adipocyte maturation; the PKA-ASK1-p38 axis facilitates uncoupling protein 1 (UCP1) induction cell-autonomously. Here, we show that ASK1 suppresses an innate immune pathway and contributes to maintenance of brown adipocytes. We report a novel chemical pull-down method for endogenous kinases using analog sensitive kinase allele (ASKA) technology and identify an ASK1 interactor in brown adipocytes, receptor-interacting serine/threonine-protein kinase 2 (RIPK2). ASK1 disrupts the RIPK2 signaling complex and inhibits the NOD-RIPK2 pathway to downregulate the production of inflammatory cytokines. As a potential biological significance, an in vitro model for intercellular regulation suggests that ASK1 facilitates the expression of UCP1 through the suppression of inflammatory cytokine production. In parallel to our previous report on the PKA-ASK1-p38 axis, our work raises the possibility of an auxiliary role of ASK1 in brown adipocyte maintenance through neutralizing the thermogenesis-suppressive effect of the NOD-RIPK2 pathway.

trans-10, cis-12, but not cis-9,trans-11 CLA isomer, inhibits brown adipocyte thermogenic capacity

2002 ◽  
Vol 282 (6) ◽  
pp. R1789-R1797 ◽  
Author(s):  
Enrique Rodrı́guez ◽  
Joan Ribot ◽  
Andreu Palou
Keyword(s):  
Linoleic Acid ◽  
Uncoupling Protein ◽  
Brown Adipocyte ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Equal Concentration ◽  
Brown Adipose ◽  
Cla Isomers ◽  
Thermogenic Capacity

Conjugated linoleic acid (CLA) is reported to have health benefits, including reduction of body fat. Previous studies have shown that brown adipose tissue (BAT) is particularly sensitive to CLA-supplemented diet feeding. Most of them use mixtures containing several CLA isomers, mainly cis-9, trans-11 and trans-10, cis-12 in equal concentration. Our aim was to characterize the separate effects of both CLA isomers on thermogenic capacity in cultured brown adipocytes. The CLA isomers showed opposite effects. Hence, on the one hand, trans-10, cis-12 inhibited uncoupling protein (UCP) 1 induction by norepinephrine (NE) and produced a decrease in leptin mRNA levels. These effects were associated with a blockage of CCAAT-enhancer-binding protein-α and peroxisome proliferator-activated receptor-γ2 mRNA expression. On the other hand, cis-9, trans-11 enhanced the UCP1 elicited by NE, an effect reported earlier for polyunsaturated fatty acids and also observed here for linoleic acid. These findings could explain, at least in part, the effects observed in vivo when feeding a CLA mixture supplemented diet as a result of the combined action of CLA isomers (reduction of adipogenesis and defective BAT thermogenesis that could be through trans-10, cis-12 and enhanced UCP1 thermogenic capacity through cis-9, trans-11).

scholarly journals Characterization of Embryonic Skin Transcriptome in Anser cygnoides at Three Feather Follicles Developmental Stages

2019 ◽  
Vol 10 (2) ◽  
pp. 443-454
Author(s):  
Chang Liu ◽  
Cornelius Tlotliso Sello ◽  
Yujian Sui ◽  
Jingtao Hu ◽  
Shaokang Chen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Developmental Stages ◽  
De Novo ◽  
Transcriptome Assembly ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Mitogen Activated Protein Kinase ◽  
Receptor Interaction ◽  
Keratinocyte Proliferation ◽  
Skin Development

In order to enrich the Anser cygnoides genome and identify the gene expression profiles of primary and secondary feather follicles development, de novo transcriptome assembly of skin tissues was established by analyzing three developmental stages at embryonic day 14, 18, and 28 (E14, E18, E28). Sequencing output generated 436,730,608 clean reads from nine libraries and de novo assembled into 56,301 unigenes. There were 2,298, 9,423 and 12,559 unigenes showing differential expression in three stages respectively. Furthermore, differentially expressed genes (DEGs) were functionally classified according to genes ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and series-cluster analysis. Relevant specific GO terms such as epithelium development, regulation of keratinocyte proliferation, morphogenesis of an epithelium were identified. In all, 15,144 DEGs were clustered into eight profiles with distinct expression patterns and 2,424 DEGs were assigned to 198 KEGG pathways. Skin development related pathways (mitogen-activated protein kinase signaling pathway, extra-cellular matrix -receptor interaction, Wingless-type signaling pathway) and genes (delta like canonical Notch ligand 1, fibroblast growth factor 2, Snail family transcriptional repressor 2, bone morphogenetic protein 6, polo like kinase 1) were identified, and eight DEGs were selected to verify the reliability of transcriptome results by real-time quantitative PCR. The findings of this study will provide the key insights into the complicated molecular mechanism and breeding techniques underlying the developmental characteristics of skin and feather follicles in Anser cygnoides.

scholarly journals Dopamine directly increases mitochondrial mass and thermogenesis in brown adipocytes

2017 ◽  
Vol 58 (2) ◽  
pp. 57-66 ◽  
Author(s):  
Rose Kohlie ◽  
Nina Perwitz ◽  
Julia Resch ◽  
Sebastian M Schmid ◽  
Hendrik Lehnert ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Energy Homeostasis ◽  
Uncoupling Protein ◽  
Brown Adipocyte ◽  
Peroxisome Proliferator ◽  
Cellular Mechanisms ◽  
Brown Adipocytes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mitochondrial Mass ◽  
Brown Adipose

Brown adipose tissue (BAT) is key to energy homeostasis. By virtue of its thermogenic potential, it may dissipate excessive energy, regulate body weight and increase insulin sensitivity. Catecholamines are critically involved in the regulation of BAT thermogenesis, yet research has focussed on the effects of noradrenaline and adrenaline. Some evidence suggests a role of dopamine (DA) in BAT thermogenesis, but the cellular mechanisms involved have not been addressed. We employed our extensively characterised murine brown adipocyte cells. D1-like and D2-like receptors were detectable at the protein level. Stimulation with DA caused an increase in cAMP concentrations. Oxygen consumption rates (OCR), mitochondrial membrane potential (Δψm) and uncoupling protein 1 (UCP1) levels increased after 24 h of treatment with either DA or a D1-like specific receptor agonist. A D1-like receptor antagonist abolished the DA-mediated effect on OCR, Δψm and UCP1. DA induced the release of fatty acids, which did not additionally alter DA-mediated increases of OCR. Mitochondrial mass (as determined by (i) CCCP- and oligomycin-mediated effects on OCR and (ii) immunoblot analysis of mitochondrial proteins) also increased within 24 h. This was accompanied by an increase in peroxisome proliferator-activated receptor gamma co-activator 1 alpha protein levels. Also, DA caused an increase in p38 MAPK phosphorylation and pharmacological inhibition of p38 MAPK abolished the DA-mediated effect on Δψm. In summary, our study is the first to reveal direct D1-like receptor and p38 MAPK-mediated increases of thermogenesis and mitochondrial mass in brown adipocytes. These results expand our understanding of catecholaminergic effects on BAT thermogenesis.

scholarly journals Small RNA Sequencing Reveals Differentially Expressed miRNAs in Necrotizing Enterocolitis in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Ren-qiang Yu ◽  
Min Wang ◽  
Shan-yu Jiang ◽  
Ying-hui Zhang ◽  
Xiao-yu Zhou ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Rna Sequencing ◽  
Necrotizing Enterocolitis ◽  
Small Rna ◽  
Mirna Expression ◽  
Expression Patterns ◽  
Wnt Signaling Pathway ◽  
Differentially Expressed ◽  
Small Rna Sequencing

Necrotizing enterocolitis (NEC) is the leading cause of death due to gastrointestinal disease in preterm infants. The role of miRNAs in NEC is still unknown. The objective of this study was to identify differentially expressed (DE) miRNAs in rats with NEC and analyze their possible roles. In this study, a NEC rat model was established using Sprague-Dawley rat pups. Small RNA sequencing was used to analyze the miRNA expression profiles in the NEC and control rats. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out to identify target mRNAs for the DE miRNAs and to explore their potential roles. The DE miRNAs were verified by real-time quantitative PCR (RT-qPCR). The status of intestinal injury and the elevated levels of inflammatory cytokines in the NEC group confirmed that the NEC model was successfully established. The 16 miRNAs were found to be differentially expressed between the NEC group and the control group of rats. Bioinformatics analysis indicated that the parental genes of the DE miRNAs were predominantly implicated in the phosphorylation, cell migration, and protein phosphorylation processes. Moreover, the DE miRNAs were mainly found to be involved in the pathways of axon guidance, endocytosis, and focal adhesion, as well as in the Wnt signaling pathway, which is related to colitis. The expression patterns of the candidate miRNAs (rno-miR-27a-5p and rno-miR-187-3p), as assessed by RT-qPCR, were in accordance with the expression patterns obtained by miRNA-sequencing. The miRNA/mRNA/pathway network revealed that rno-miR-27a-5p and rno-miR-187-3p might be involved in NEC via the Wnt signaling pathway. We found an altered miRNA expression pattern in rats with NEC. We hypothesize that rno-miR-27a-5p and rno-miR-187-3p might mediate the NEC pathophysiological processes via the Wnt signaling pathway.

Characterization of Wnt signaling pathway (WSP) aberrations in advanced prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 203-203
Author(s):  
Fady Ghali ◽  
Devin Patel ◽  
Christina Jamieson ◽  
J Kellogg Parsons ◽  
Rana R. McKay
Keyword(s):  
Prostate Cancer ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
De Novo ◽  
Wnt Signaling Pathway ◽  
Treatment Strategies ◽  
Activating Mutations ◽  
Disease Characteristics ◽  
Activating Mutation ◽  
Visceral Metastases

203 Background: Aberrations in Wnt signaling pathway (WSP) are implicated in disease progression and resistance of multiple malignancies including prostate cancer (PCa). We sought to characterize the clinical phenotype and molecular genotype of PCa patients with WSP alterations. Methods: Eligible patients included those with PCa having undergone clinical-grade next generation DNA sequencing of tumor derived from prostate or metastasis tissue. We identified patients with somatic activating mutations in CTNNB1 and RSPO2, or inactivating mutations in APC, RNF43, or ZNRF3. Patient and disease characteristics were collected. Clinical and outcome parameters were associated with WSP mutation status using STATA(V. 13.1, College Station, Texas). Results: A total of 169 patients were identified of whom 29 (18.1%) had a WSP activating mutation. Median age of the overall cohort was 64.85 (IQR 56.77, 70.36). 115 (68.0%) patients had Gleason 8-10 disease, 34 (20.1%) presented with de novo metastatic disease, 85 (50.3%) developed CRPC and 23 (13.6%) developed visceral metastases. Clinical characteristics were similar between biomarker groups. There was no association with the presence of a Wnt activating mutation and RB1, p53, pTEN, or BRCA1/2 alteration. Median time to CRPC was 39.42 (IQR 14.50 – 87.52) and 24.39 (IQR 14.99 – 46.03) months for no-WSP and WSP-aberrant respectively. Median 5-year OS was 83.7% (95% CI 73.0-90.4%) and 79.6% (95% CI 52.9 – 92.2%) months for no-WSP and WSP-aberrant respectively. Table evaluates biomarker status with time to CRPC development and overall survival (OS). Conclusions: We observe that somatic WSP activating mutations are present in 18.1% of patients with mPCa, consist with prior reports. Understanding the clinical significance of WSP alterations is critical to inform treatment strategies in patients with advanced disease.[Table: see text]

scholarly journals Norepinephrine, tri-iodothyronine and insulin upregulate glyceraldehyde-3-phosphate dehydrogenase mRNA during Brown adipocyte differentiation

1999 ◽  
pp. 169-179 ◽  
Author(s):  
I Barroso ◽  
B Benito ◽  
C Garci-Jimenez ◽  
A Hernandez ◽  
MJ Obregon ◽  
...  
Keyword(s):  
De Novo ◽  
Precursor Cells ◽  
Brown Adipocyte ◽  
Mrna Levels ◽  
Brown Adipocytes ◽  
Gapdh Gene ◽  
Gapdh Mrna ◽  
Brown Adipose ◽  
Dose Dependent ◽  
De Novo Protein Synthesis

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene expression was studied in differentiating brown adipocytes. Northern blot analysis showed that GAPDH mRNA levels increased during differentiation of precursor cells into mature adipocytes, mainly in the initial stages of the differentiation process. Insulin, tri-iodothyronine (T(3)) and norepinephrine, the main regulators of brown adipose tissue function, upregulated GAPDH mRNA levels, whereas retinoic acid inhibited them. The effect of insulin was present on all culture days examined, was time- and dose-dependent, and was exerted through its own receptors, as demonstrated by comparing insulin and insulin-like growth factor (IGF)-I and -II potencies in this system. Using the transcriptional inhibitor, actinomycin D, we demonstrated that T(3), and to a lesser extent insulin, stabilized GAPDH mRNA. Experiments with cycloheximide indicated that both hormones require de novo protein synthesis to achieve their effects. Using cAMP analogs, we showed that the effect of norepinephrine is probably exerted through this second messenger. Co-operation was elucidated between norepinephrine- and insulin-mediated induction of GAPDH mRNA levels. In summary, we have demonstrated that GAPDH mRNA is subjected to multifactorial regulation in differentiating brown adipocytes that includes differentiation of precursor cells and the lipogenic/lipolytic regulators of the tissue.

scholarly journals Diagnosis and Prognostic Value of SPARC in Gastric Carcinoma: database mining for GCTA

2020 ◽  
Author(s):  
Diqi Ying ◽  
Ding Li ◽  
Xiao Jin
Keyword(s):  
Gastric Carcinoma ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Wnt Signaling Pathway ◽  
Mapk Signaling ◽  
Gene Set Enrichment Analysis ◽  
Signal Pathways ◽  
Potential Biomarker ◽  
Incidence And Mortality ◽  
Sparc Expression

Abstract Gastric carcinoma (GC) remains high incidence and mortality both in developed and developing countries. SPARC is extracellular non-structural matrix glycoprotein. Previous studies were closely associated with bone disease. However, the role of SPARC in GC remains largely unclear. In our study, we explored the diagnosis, prognosis and pathway enrichments value of SPARC in GC. Here, with the data from The Cancer Genome Atlas (TCGA), we used receiver operating characteristic (ROC) curve analysis to estimate the diagnosis value of the SPARC expression, Univariate and multivariate analysis to the prognosis, Gene set enrichment analysis (GSEA) to the signal pathway enrichments. As a result, SPARC expression was significantly higher in the GC tissue samples. Those with high SPARC expression of GC patients were worse prognosis. GSEA shows the gene sets related signal pathways including transforming growth factor (TGF) beta signaling pathway, pathways in cancer, Wnt signaling pathway, Mitogen-activated protein kinase (MAPK) signaling pathway etc. In brief, those results suggest that SPARC can serve as a potential biomarker for GC in diagnosis and prognosis.

Thermogenically competent nonadrenergic recruitment in brown preadipocytes by a PPARγ agonist

2008 ◽  
Vol 295 (2) ◽  
pp. E287-E296 ◽  
Author(s):  
Natasa Petrovic ◽  
Irina G. Shabalina ◽  
James A. Timmons ◽  
Barbara Cannon ◽  
Jan Nedergaard
Keyword(s):  
Primary Cultures ◽  
Brown Adipocyte ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Sympathetic Stimulation ◽  
Promoting Effect ◽  
Brown Adipocytes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist ◽  
Brown Adipose

Most physiologically induced examples of recruitment of brown adipose tissue (BAT) occur as a consequence of chronic sympathetic stimulation (norepinephrine release within the tissue). However, in some physiological contexts (e.g., prenatal and prehibernation recruitment), this pathway is functionally contraindicated. Thus a nonsympathetically mediated mechanism of BAT recruitment must exist. Here we have tested whether a PPARγ activation pathway could competently recruit BAT, independently of sympathetic stimulation. We continuously treated primary cultures of mouse brown (pre)adipocytes with the potent peroxisome proliferator-activated receptor-γ (PPARγ) agonist rosiglitazone. In rosiglitazone-treated cultures, morphological signs of adipose differentiation and expression levels of the general adipogenic marker aP2 were manifested much earlier than in control cultures. Importantly, in the presence of the PPARγ agonist the brown adipocyte phenotype was significantly enhanced: UCP1 was expressed even in the absence of norepinephrine, and PPARα expression and norepinephrine-induced PGC-1α mRNA levels were significantly increased. However, the augmented levels of PPARα could not explain the brown-fat promoting effect of rosiglitazone, as this effect was still evident in PPARα-null cells. In continuously rosiglitazone-treated brown adipocytes, mitochondriogenesis, an essential part of BAT recruitment, was significantly enhanced. Most importantly, these mitochondria were capable of thermogenesis, as rosiglitazone-treated brown adipocytes responded to the addition of norepinephrine with a large increase in oxygen consumption. This thermogenic response was not observable in rosiglitazone-treated brown adipocytes originating from UCP1-ablated mice; hence, it was UCP1 dependent. Thus the PPARγ pathway represents an alternative, potent, and fully competent mechanism for BAT recruitment, which may be the cellular explanation for the enigmatic recruitment in prehibernation and prenatal states.

scholarly journals Repeated Oral Administration of Flavan-3-ols Induces Browning in Mice Adipose Tissues Through Sympathetic Nerve Activation

2021 ◽  
Author(s):  
Yuko Ishii ◽  
Orie Muta ◽  
Tomohiro Teshima ◽  
Nayuta Hirasima ◽  
Minayu Odaka ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Transmembrane Protein ◽  
Repeated Administration ◽  
Peroxisome Proliferator ◽  
Adipose Tissues ◽  
Peroxisome Proliferator Activated Receptor ◽  
Brown Adipose ◽  
Sympathetic Nerve Activation ◽  
Pr Domain ◽  
The Impact

We previously found increases in uncoupling protein (Ucp)-1 transcription in brown adipose tissue (BAT) of mice following a single oral dose of flavan 3-ols (FL), a fraction of catechins and procyanidins. It was confirmed that these changes were totally reduced by co-treatment of adrenaline blockers. According to these previous results, FL possibly activates sympathetic nervous system (SNS). In this study, we confirmed the marked increase in urinary catecholamine (CA) s projecting SNS activity following a single dose of 50 mg/kg FL. In addition, we examined the impact of the repeated administration of 50 mg/kg FL for 14 days on adipose tissues in mice. In BAT, FL tended to increase the level of Ucp-1 along with thermogenic transcriptome factors, such as peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and PR domain-containing (PRDM)1. Transcription of browning markers, such as CD137 and transmembrane protein (TMEM) 26 in addition to PGC-1α were increased in epididymal adipose (eWAT) by FL. A multilocular morphology with cell size reduction was shown in the inguinal adipose (iWAT), together with increasing the level of Ucp-1 following administration of FL. These results suggest that FL produces browning in adipose through activation of the SNS.

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