scholarly journals Multi-Omics Analysis of Diabetic Heart Disease in the db/db Model Reveals Potential Targets for Treatment by a Longevity-Associated Gene

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1283
Author(s):  
Ashton Faulkner ◽  
Zexu Dang ◽  
Elisa Avolio ◽  
Anita C Thomas ◽  
Thomas Batstone ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
High Performance ◽  
Bioinformatic Analysis ◽  
Differentially Expressed ◽  
Metabolic Phenotype ◽  
Diabetic Heart ◽  
Diabetic Mice ◽  
Diabetic Heart Disease ◽  
Adverse Influence ◽  
Related Proteins

Characterisation of animal models of diabetic cardiomyopathy may help unravel new molecular targets for therapy. Long-living individuals are protected from the adverse influence of diabetes on the heart, and the transfer of a longevity-associated variant (LAV) of the human BPIFB4 gene protects cardiac function in the db/db mouse model. This study aimed to determine the effect of LAV-BPIFB4 therapy on the metabolic phenotype (ultra-high-performance liquid chromatography-mass spectrometry, UHPLC-MS) and cardiac transcriptome (next-generation RNAseq) in db/db mice. UHPLC-MS showed that 493 cardiac metabolites were differentially modulated in diabetic compared with non-diabetic mice, mainly related to lipid metabolism. Moreover, only 3 out of 63 metabolites influenced by LAV-BPIFB4 therapy in diabetic hearts showed a reversion from the diabetic towards the non-diabetic phenotype. RNAseq showed 60 genes were differentially expressed in hearts of diabetic and non-diabetic mice. The contrast between LAV-BPIFB4- and vehicle-treated diabetic hearts revealed eight genes differentially expressed, mainly associated with mitochondrial and metabolic function. Bioinformatic analysis indicated that LAV-BPIFB4 re-programmed the heart transcriptome and metabolome rather than reverting it to a non-diabetic phenotype. Beside illustrating global metabolic and expressional changes in diabetic heart, our findings pinpoint subtle changes in mitochondrial-related proteins and lipid metabolism that could contribute to LAV-BPIFB4-induced cardio-protection in a murine model of type-2 diabetes.

P1889Quantitative global proteomics and lysine acetylome analysis of changes in left atrial appendage tissue from valvular heart disease patients with atrial fibrillation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Tu ◽  
F Qin ◽  
F Bai ◽  
Y Xiao ◽  
X Liao ◽  
...  
Keyword(s):  
Heart Disease ◽  
Energy Metabolism ◽  
Valvular Heart Disease ◽  
Left Atrial ◽  
Left Atrial Appendage ◽  
Interaction Network ◽  
Bioinformatic Analysis ◽  
Cardiac Contraction ◽  
Differentially Expressed ◽  
Related Proteins

Abstract Background Previous studies have shown that acetylation plays a critical role in regulating the progress of cardiovascular diseases by acetylated histone and non-histones protein. However, the global lysine acetylome during atrial fibrillation (AF) were not fully understood. Purpose The aim of the present study was to identify the underlying mechanisms of AF via profiling of the quantitative changes of global proteomics and lysine acetylome in the left atrial appendage (LAA) tissues from valvular heart disease patients with AF. Methods This study obtained LAA specimens from patients undergoing cardiac surgery for severe valvular heart disease. The LAA specimens were obtained from both 9 patients with AF and with sinus rhythm (SR). The changes of proteome and acetylome in the AF-LAA vs SR-LAA tissues were studied using dimethyl-labeling, HPLC fractionation, affinity enrichment, LC-MS/MS analysis, database Search and bioinformatic analysis. The acetylated levels of each lysine acetylated site were normalized on the basis of the corresponding protein abundance. Results The bioinformatic analysis indicates 294 up-regulated (AF/SR ratio >1.3) proteins and 169 down-regulated (AF/SR ratio <1/1.3) proteins in the AF-LAA vs SR-LAA were detected. Moreover, 3,880 sites in 1,044 proteins were quantified. Motif analysis of the identified acetylated peptides indicated that a total of 14 significantly enriched amino acid sequence motifs from −10 to +10 surrounding the acetylated lysine (Kac) were defined according to 3412 peptides from 1115 proteins. Among the quantified acetylated sites and proteins, 231 up-regulated acetylated sites in 130 proteins and 121 down-regulated acetylated sites in 74 proteins were detected. The enrichment-based clustering analysis showed that energy metabolism and cardiac contraction-related proteins were highly differentially expressed in the AF-LAA vs SR-LAA. Meanwhile, the protein-protein interaction network of the differentially expressed acetylated proteins demonstrated that there were 146 nodes and 569 interactions in the network and quite a lot of interactions in energy metabolism-related proteins and in cardiac contraction-related proteins. Furthermore, the acetylated levels of most differentially expressed energy metabolism-related proteins involving in oxidative phosphorylation, TCA cycle, respiratory ETC, fatty acid metabolism were up-regulated. On the contrary, the acetylated levels of most acetylated sites in differentially expressed cardiac contraction-related proteins including the key contraction proteins were down-regulated. Interaction network of Ac-proteins Conclusions This study details and expands our understanding of the changes of proteome and lysine acetylome in the LAA tissues from valvular heart disease patients with AF. The data suggest important expression differences of acetylated proteins related to energy metabolism and cardiac contraction which may be involved in the matrix of AF formation and maintainence. Acknowledgement/Funding This work was supported by the grants from the National Natural Science Foundation of China (no. 81600273, no. 81570310, no.81770337 and no.81870258)

1060-P: The Effect of FGF21/GLP-1 Fusion Protein on Glucose and Lipid Metabolism Using Diabetic Mice Models

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1060-P
Author(s):  
LIXIN GUO ◽  
QI PAN ◽  
CHAO CHEN ◽  
SHUSHAN LIN ◽  
YU LI ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Fusion Protein ◽  
Diabetic Mice ◽  
Glucose And Lipid Metabolism

scholarly journals Sex-Biased lncRNA Signature in Fetal Growth Restriction (FGR)

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 921
Author(s):  
Aleksandra Lipka ◽  
Jan Pawel Jastrzebski ◽  
Lukasz Paukszto ◽  
Karol Gustaw Makowczenko ◽  
Elzbieta Lopienska-Biernat ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Target Genes ◽  
Active Regions ◽  
Bioinformatic Analysis ◽  
Growth Restriction ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Differential Analysis ◽  
Protein Coding

Impaired fetal growth is one of the most important causes of prematurity, stillbirth and infant mortality. The pathogenesis of idiopathic fetal growth restriction (FGR) is poorly understood but is thought to be multifactorial and comprise a range of genetic causes. This research aimed to investigate non-coding RNAs (lncRNAs) in the placentas of male and female fetuses affected by FGR. RNA-Seq data were analyzed to detect lncRNAs, their potential target genes and circular RNAs (circRNAs); a differential analysis was also performed. The multilevel bioinformatic analysis enabled the detection of 23,137 placental lncRNAs and 4263 of them were classified as novel. In FGR-affected female fetuses’ placentas (ff-FGR), among 19 transcriptionally active regions (TARs), five differentially expressed lncRNAs (DELs) and 12 differentially expressed protein-coding genes (DEGs) were identified. Within 232 differentially expressed TARs identified in male fetuses (mf-FGR), 33 encompassed novel and 176 known lncRNAs, and 52 DEGs were upregulated, while 180 revealed decreased expression. In ff-FGR ACTA2-AS1, lncRNA expression was significantly correlated with five DEGs, and in mf-FGR, 25 TARs were associated with DELs correlated with 157 unique DEGs. Backsplicing circRNA processes were detected in the range of H19 lncRNA, in both ff- and mf-FGR placentas. The performed global lncRNAs characteristics in terms of fetal sex showed dysregulation of DELs, DEGs and circRNAs that may affect fetus growth and pregnancy outcomes. In female placentas, DELs and DEGs were associated mainly with the vasculature, while in male placentas, disturbed expression predominantly affected immune processes.

scholarly journals Characterization of Differentially Expressed Circulating miRNAs in Metabolically Healthy versus Unhealthy Obesity

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 321
Author(s):  
Susana Rovira-Llopis ◽  
Rubén Díaz-Rúa ◽  
Carmen Grau-del Valle ◽  
Francesca Iannantuoni ◽  
Zaida Abad-Jimenez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Metabolism ◽  
Insulin Signalling ◽  
Cross Sectional Study ◽  
Differentially Expressed ◽  
Circulating Mirnas ◽  
Oxidative Stress Biomarkers ◽  
Cross Sectional ◽  
Metabolically Healthy Obese ◽  
Metabolically Healthy

Obese individuals without metabolic comorbidities are categorized as metabolically healthy obese (MHO). MicroRNAs (miRNAs) may be implicated in MHO. This cross-sectional study explores the link between circulating miRNAs and the main components of metabolic syndrome (MetS) in the context of obesity. We also examine oxidative stress biomarkers in MHO vs. metabolically unhealthy obesity (MUO). We analysed 3536 serum miRNAs in 20 middle-aged obese individuals: 10 MHO and 10 MUO. A total of 159 miRNAs were differentially expressed, of which, 72 miRNAs (45.2%) were higher and 87 miRNAs (54.7%) were lower in the MUO group. In addition, miRNAs related to insulin signalling and lipid metabolism pathways were upregulated in the MUO group. Among these miRNAs, hsa-miR-6796-5p and hsa-miR-4697-3p, which regulate oxidative stress, showed significant correlations with glucose, triglycerides, HbA1c and HDLc. Our results provide evidence of a pattern of differentially expressed miRNAs in obesity according to MetS, and identify those related to insulin resistance and lipid metabolism pathways.

scholarly journals High-throughput screening of circRNAs reveals novel mechanisms of tuberous sclerosis complex-related renal angiomyolipoma

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Yang Zhao ◽  
Hao Guo ◽  
Wenda Wang ◽  
Guoyang Zheng ◽  
Zhan Wang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Regulatory Network ◽  
High Throughput Screening ◽  
Kidney Tissue ◽  
Cell Types ◽  
The Body ◽  
Differentially Expressed ◽  
Renal Angiomyolipoma

Abstract Objective Tuberous sclerosis complex (TSC) is a rare autosomal dominant disease characterized by lesions throughout the body. Our previous study showed the abnormal up-regulation of miRNAs plays an important part in the pathogenesis of TSC-related renal angiomyolipoma (TSC-RAML). circRNAs were known as important regulators of miRNA, but little is known about the circRNAs in TSC-RAMLs. Methods Microarray chips and RNA sequencing were used to identify the circRNAs and mRNAs that were differently expressed between the TSC-RAML and normal kidney tissue. A competitive endogenous RNA (ceRNA) regulatory network was constructed to reveal the regulation of miRNAs and mRNAs by the circRNAs. The biological functions of circRNA and mRNA were analyzed by pathway analysis. Microenvironmental cell types were estimated with the MCP-counter package. Results We identified 491 differentially expressed circRNAs (DECs) and 212 differentially expressed genes (DEGs), and 6 DECs were further confirmed by q-PCR. A ceRNA regulatory network which included 6 DECs, 5 miRNAs, and 63 mRNAs was established. Lipid biosynthetic process was significantly up-regulated in TSC-RAML, and the humoral immune response and the leukocyte chemotaxis pathway were found to be down-regulated. Fibroblasts are enriched in TSC-RAML, and the up-regulation of circRNA_000799 and circRNA_025332 may be significantly correlated to the infiltration of the fibroblasts. Conclusion circRNAs may regulate the lipid metabolism of TSC-RAML by regulation of the miRNAs. Fibroblasts are enriched in TSC-RAMLs, and the population of fibroblast may be related to the alteration of circRNAs of TSC-RAML. Lipid metabolism in fibroblasts is a potential treatment target for TSC-RAML.

scholarly journals Expression of lipid metabolism-related proteins in breast phyllodes tumors

Neoplasma ◽  
2016 ◽  
Author(s):  
Y. Y. JUNG ◽  
Y. K. LEE ◽  
J. S. KOO
Keyword(s):  
Lipid Metabolism ◽  
Phyllodes Tumors ◽  
Related Proteins

scholarly journals Polyphenol Supplementation Reverses Age-Related Changes in Microglial Signaling Cascades

2021 ◽  
Vol 22 (12) ◽  
pp. 6373
Author(s):  
Ahmad Jalloh ◽  
Antwoine Flowers ◽  
Charles Hudson ◽  
Dale Chaput ◽  
Jennifer Guergues ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Control Diet ◽  
Bioinformatic Analysis ◽  
Diet Group ◽  
Differentially Expressed ◽  
Signaling Cascades ◽  
Complex Nature ◽  
Differentially Expressed Proteins ◽  
Ms Analysis ◽  
Age Related

Microglial activity in the aging neuroimmune system is a central player in aging-related dysfunction. Aging alters microglial function via shifts in protein signaling cascades. These shifts can propagate neurodegenerative pathology. Therapeutics require a multifaceted approach to understand and address the stochastic nature of this process. Polyphenols offer one such means of rectifying age-related decline. Our group used mass spectrometry (MS) analysis to explicate the complex nature of these aging microglial pathways. In our first experiment, we compared primary microglia isolated from young and aged rats and identified 197 significantly differentially expressed proteins between these groups. Then, we performed bioinformatic analysis to explore differences in canonical signaling cascades related to microglial homeostasis and function with age. In a second experiment, we investigated changes to these pathways in aged animals after 30-day dietary supplementation with NT-020, which is a blend of polyphenols. We identified 144 differentially expressed proteins between the NT-020 group and the control diet group via MS analysis. Bioinformatic analysis predicted an NT-020 driven reversal in the upregulation of age-related canonical pathways that control inflammation, cellular metabolism, and proteostasis. Our results highlight salient aspects of microglial aging at the level of protein interactions and demonstrate a potential role of polyphenols as therapeutics for age-associated dysfunction.

Effects of low-carbohydrate diet and ketogenic diet on glucose and lipid metabolism in type 2 diabetic mice

Nutrition ◽  
2021 ◽  
pp. 111230
Author(s):  
Zi Yang ◽  
Jingyi Mi ◽  
Yu Wang ◽  
Lamei Xue ◽  
Jinxin Liu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Ketogenic Diet ◽  
Diabetic Mice ◽  
Carbohydrate Diet ◽  
Low Carbohydrate Diet ◽  
Glucose And Lipid Metabolism ◽  
Low Carbohydrate ◽  
Type 2 Diabetic

scholarly journals Regulation of Metabolic Reprogramming by Long Non-Coding RNAs in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3485
Author(s):  
Assunta Sellitto ◽  
Giovanni Pecoraro ◽  
Giorgio Giurato ◽  
Giovanni Nassa ◽  
Francesca Rizzo ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Cancer Cells ◽  
Metabolic Reprogramming ◽  
Metabolic Phenotype ◽  
Metabolic Alterations ◽  
Cell Proliferation And Differentiation ◽  
Non Coding Rna ◽  
Proliferation And Differentiation ◽  
Non Coding Rnas ◽  
Additional Level

Metabolic reprogramming is a well described hallmark of cancer. Oncogenic stimuli and the microenvironment shape the metabolic phenotype of cancer cells, causing pathological modifications of carbohydrate, amino acid and lipid metabolism that support the uncontrolled growth and proliferation of cancer cells. Conversely, metabolic alterations in cancer can drive changes in genetic programs affecting cell proliferation and differentiation. In recent years, the role of non-coding RNAs in metabolic reprogramming in cancer has been extensively studied. Here, we review this topic, with a focus on glucose, glutamine, and lipid metabolism and point to some evidence that metabolic alterations occurring in cancer can drive changes in non-coding RNA expression, thus adding an additional level of complexity in the relationship between metabolism and genetic programs in cancer cells.

Comparison of the effects of raw and cooked adzuki bean on glucose/lipid metabolism and liver function in diabetic mice

2021 ◽  
Author(s):  
Qingyu Zhao ◽  
Dianzhi Hou ◽  
Laraib Yousaf ◽  
Yong Xue ◽  
Qun Shen
Keyword(s):  
Lipid Metabolism ◽  
Liver Function ◽  
Adzuki Bean ◽  
Diabetic Mice
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