scholarly journals The Small GTPases Rab27b Regulates Mitochondrial Fatty Acid Oxidative Metabolism of Cardiac Mesenchymal Stem Cells

2020 ◽  
Vol 8 ◽  
Author(s):  
Yue Jin ◽  
Yan Shen ◽  
Xuan Su ◽  
Jingwen Cai ◽  
Yutao Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Fatty Acid ◽  
Oxidative Metabolism ◽  
Small Gtpases ◽  
Mitochondrial Fatty Acid

scholarly journals RNAase III-Type Enzyme Dicer Regulates Mitochondrial Fatty Acid Oxidative Metabolism in Cardiac Mesenchymal Stem Cells

2019 ◽  
Vol 20 (22) ◽  
pp. 5554 ◽  
Author(s):  
Xuan Su ◽  
Yue Jin ◽  
Yan Shen ◽  
Il-man Kim ◽  
Neal L. Weintraub ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Oxidative Phosphorylation ◽  
Oxidative Metabolism ◽  
Gene Deletion ◽  
Aerobic Glycolysis ◽  
Critical Role ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Metabolic Switch ◽  
Mitochondrial Fatty Acid

Cardiac mesenchymal stem cells (C-MSC) play a key role in maintaining normal cardiac function under physiological and pathological conditions. Glycolysis and mitochondrial oxidative phosphorylation predominately account for energy production in C-MSC. Dicer, a ribonuclease III endoribonuclease, plays a critical role in the control of microRNA maturation in C-MSC, but its role in regulating C-MSC energy metabolism is largely unknown. In this study, we found that Dicer knockout led to concurrent increase in both cell proliferation and apoptosis in C-MSC compared to Dicer floxed C-MSC. We analyzed mitochondrial oxidative phosphorylation by quantifying cellular oxygen consumption rate (OCR), and glycolysis by quantifying the extracellular acidification rate (ECAR), in C-MSC with/without Dicer gene deletion. Dicer gene deletion significantly reduced mitochondrial oxidative phosphorylation while increasing glycolysis in C-MSC. Additionally, Dicer gene deletion selectively reduced the expression of β-oxidation genes without affecting the expression of genes involved in the tricarboxylic acid (TCA) cycle or electron transport chain (ETC). Finally, Dicer gene deletion reduced the copy number of mitochondrially encoded 1,4-Dihydronicotinamide adenine dinucleotide (NADH): ubiquinone oxidoreductase core subunit 6 (MT-ND6), a mitochondrial-encoded gene, in C-MSC. In conclusion, Dicer gene deletion induced a metabolic shift from oxidative metabolism to aerobic glycolysis in C-MSC, suggesting that Dicer functions as a metabolic switch in C-MSC, which in turn may regulate proliferation and environmental adaptation.

The role of albumin and PPAR-αin differentiation-dependent change of fatty acid profile during differentiation of mesenchymal stem cells to hepatocyte-like cells

2014 ◽  
pp. n/a-n/a ◽  
Author(s):  
Shahnaz Esmaeli ◽  
Abdolamir Allameh ◽  
Masoud Soleimani ◽  
Fatemeh Rahbarizadeh ◽  
Mehdi Frouzandeh-Moghadam
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Fatty Acid ◽  
Fatty Acid Profile ◽  
Dependent Change

scholarly journals Alteration of fatty acid oxidation by increased CPT1A on replicative senescence of placenta-derived mesenchymal stem cells

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jin Seok ◽  
Hyun Sook Jung ◽  
Sohae Park ◽  
Jung Ok Lee ◽  
Chong Jai Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Fatty Acid ◽  
Mitochondrial Dysfunction ◽  
Fatty Acid Oxidation ◽  
Replicative Senescence ◽  
Acid Oxidation ◽  
Differentiation Potential ◽  
Passage Number

Abstract Background Human placenta-derived mesenchymal stem cells (PD-MSCs) are powerful sources for cell therapy in regenerative medicine. However, a limited lifespan by senescence through mechanisms that are well unknown is the greatest obstacle. In the present study, we first demonstrated the characterization of replicative senescent PD-MSCs and their possible mitochondrial functional alterations. Methods Human PD-MSCs were cultured to senescent cells for a long period of time. The cells of before passage number 8 were early cells and after passage number 14 were late cells. Also, immortalized cells of PD-MSCs (overexpressed hTERT gene into PD-MSCs) after passage number 14 were positive control of non-senescent cells. The characterization and mitochondria analysis of PD-MSCs were explored with long-term cultivation. Results Long-term cultivation of PD-MSCs exhibited increases of senescent markers such as SA-β-gal and p21 including apoptotic factor, and decreases of proliferation, differentiation potential, and survival factor. Mitochondrial dysfunction was also observed in membrane potential and metabolic flexibility with enlarged mitochondrial mass. Interestingly, we founded that fatty acid oxidation (FAO) is an important metabolism in PD-MSCs, and carnitine palmitoyltransferase1A (CPT1A) overexpressed in senescent PD-MSCs. The inhibition of CPT1A induced a change of energy metabolism and reversed senescence of PD-MSCs. Conclusions These findings suggest that alteration of FAO by increased CPT1A plays an important role in mitochondrial dysfunction and senescence of PD-MSCs during long-term cultivation.

scholarly journals LncRNA HCG11 Inhibits Adipocyte Differentiation in Human Adipose-Derived Mesenchymal Stem Cells by Sponging miR-204-5p to Upregulate SIRT1

2020 ◽  
Vol 29 ◽  
pp. 096368972096809
Author(s):  
Dandan Li ◽  
Yang Liu ◽  
Wei Gao ◽  
Jiakai Han ◽  
Rongrong Yuan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Fatty Acid ◽  
Reporter Gene ◽  
Adipocyte Differentiation ◽  
Gene Analysis ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Reporter Gene Analysis ◽  
Adipogenic Marker

Long noncoding RNAs (lncRNAs) have been discovered to play a key role in adipogenesis, while the role of lncRNA human leukocyte antigen complex group 11 (HCG11) in adipocyte differentiation has not been studied clearly. We used human adipose-derived mesenchymal stem cells (hAdMSCs) to establish a model of cell differentiation in vitro and found that expression of lncRNA HCG11 was decreased during adipogenesis through real-time quantitative polymerase chain reaction analysis. Then, hAdMSCs were transfected with pcDNA-HCG11 or HCG11-shRNA (sh-HCG11); the adipogenic marker proteins were detected by Western blot, and the activity of lipogenesis enzymes was detected by spectrophotometry. The expression of CCAAT-enhancer-binding protein α, fatty acid-binding protein, peroxisome proliferator-activated receptor gamma 2 and the levels of acetyl coenzyme A carboxylase and fatty acid synthase FAS were significantly downregulated in hAdMSCs at different stages transfected with pcDNA-HCG11, while knockdown of lncRNA HCG11 promoted adipocyte differentiation. Bioinformatic analysis indicated that miR-204-5p was a potential target gene of HCG11, which was confirmed by luciferase reporter gene analysis and RNA pull-down analysis. In addition, miR-204-5p directly targeting the 3′-untranslated region of SIRT1 was also predicted by StarBase and verified by luciferase reporter gene analysis. Enforced expression of miR-204-5p negatively regulated the SIRT1 protein level. Furthermore, SIRT1 overexpression significantly inhibited adipogenic marker protein, levels of lipogenesis enzymes, and the proliferation of hAdMSCs. When pcDNA-HCG11 and miR-204-5p mimic were co-transfected into hAdMSCs, we found that the miR-204-5p mimic reversed the suppressor effect of pcDNA-HCG11. Taken together, we found that HCG11 negatively regulated cell proliferation and adipogenesis by the miR-204-5p/SIRT1 axis. Our findings might provide a new target for the study of adipogenesis in hAdMSCs and obesity.

scholarly journals Continuous and Uninterrupted Oxygen Tension Influences the Colony Formation and Oxidative Metabolism of Human Mesenchymal Stem Cells

2013 ◽  
Vol 19 (1) ◽  
pp. 68-79 ◽  
Author(s):  
Girish Pattappa ◽  
Stephen D. Thorpe ◽  
Nick C. Jegard ◽  
Hannah K. Heywood ◽  
Joost D. de Bruijn ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Oxygen Tension ◽  
Oxidative Metabolism ◽  
Colony Formation ◽  
Human Mesenchymal Stem Cells

scholarly journals GNPDA2 Gene Affects Adipogenesis and Alters the Transcriptome Profile of Human Adipose-Derived Mesenchymal Stem Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Lijun Wu ◽  
Feifei Ma ◽  
Xiaoyuan Zhao ◽  
Mei-Xian Zhang ◽  
Jianxin Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Fatty Acid ◽  
Glucose Metabolism ◽  
Signaling Pathway ◽  
Lipid Droplets ◽  
Association Studies ◽  
Enrichment Analysis ◽  
Genome Wide Association Studies ◽  
Transcriptome Profile

Background. Genome-wide association studies have found an obesity-related single-nucleotide polymorphism rs10938397 near the glucosamine-6-phosphate deaminase 2 gene (GNPDA2) encoding, an enzyme that catalyzes the deamination of the glucosamine-6-phosphate involved in the hexosamine signaling pathway, but the molecular mechanisms underlying the missing link between GNPDA2 and obesity remain elusive. Methods. As obesity is accompanied by an increase in the size and the number of adipocytes, the present study investigates the possible mechanism of the GNPDA2 in adipogenesis using GeneChip® Human Transcriptome Array 2.0 in human adipose-derived mesenchymal stem cells. Results. We found that overexpression of GNPDA2 enhanced accumulation of lipid droplets, and knocking down the gene decreased accumulation of lipid droplets. GO term enrichment analysis indicated that most differentially expressed genes (DEGs) affected by deficiency of GNPDA2 have functions to lipid and glucose metabolism. Further KEGG enrichment analysis showed that the greatest proportion of DEGs are involved in thermogenesis, peroxisome proliferator-activated receptor (PPAR) signaling pathway, carbon metabolism, and fatty acid metabolism including fatty acid degradation, elongation, and biosynthesis. Conclusion. These findings suggest that GNPDA2 may be a critical gene for lipid and glucose metabolism, and the expression level of GNPDA2 alters the transcriptome profile of human adipose-derived mesenchymal stem cells.

New Insights into Apolipoprotein A5 and the Modulation of Human Adipose-derived Mesenchymal Stem Cells Adipogenesis

2020 ◽  
Vol 20 (2) ◽  
pp. 144-156 ◽  
Author(s):  
Xin Su ◽  
Shuwei Weng ◽  
Daoquan Peng
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Fatty Acid ◽  
Fatty Acid Synthetase ◽  
Loss Of Function ◽  
Related Factors ◽  
Fatty Acid Binding ◽  
Apolipoprotein A5 ◽  
Underlying Mechanisms ◽  
Excessive Accumulation

Background: The hallmark of obesity is the excessive accumulation of triglyceride (TG) in adipose tissue. Apolipoprotein A5 (ApoA5) has been shown to influence the prevalence and pathogenesis of obesity. However, the underlying mechanisms remain to be clarified. Methods: Human adipose-derived mesenchymal stem cells (AMSCs) were treated with 600 ng/ml human recombinant ApoA5 protein. The effect of ApoA5 on intracellular TG content and adipogenic related factors expression were determined. Furthermore, the effect of ApoA5 on CIDE-C expression was also observed. Results: During the process of adipogenesis, ApoA5 treatment reduced the intracellular accumulation of lipid droplets and the TG levels; meanwhile, ApoA5 down-regulated the expression levels of adipogenic related factors, including CCAAT enhancer-binding proteins α/β (C/EBPα/β), fatty acid synthetase (FAS), and fatty acid-binding protein 4 (FABP4). Furthermore, the suppression of adipogenesis by ApoA5 was mediated through the inhibition of CIDE-C expression, an important factor which promotes the process of adipogenesis. However, over-expressing intracellular CIDE-C could lead to the loss-of-function of ApoA5 in inhibiting AMSCs adipogenesis. Conclusions: In conclusion, ApoA5 inhibits the adipogenic process of AMSCs through, at least partly, down-regulating CIDE-C expression. The present study provides novel mechanisms whereby ApoA5 prevents obesity via AMSCs in humans.

scholarly journals Inhibition of PPARγ Gene Particle Downregulates the Differentiation of Rabbit Bone Marrow Mesenchymal Stem Cells into Adipocytes

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Yi Dong ◽  
Long Chang ◽  
Long Hei ◽  
Sensen Yang ◽  
Wenxin Ma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Fatty Acid ◽  
Control Group ◽  
Expression Levels ◽  
Triacylglycerol Content ◽  
Marrow Mesenchymal Stem Cells ◽  
Rabbit Bone ◽  
Pparγ Gene

This study aims to evaluate the effect of peroxisome proliferator-activated receptor (PPAR) γ gene inhibition on the adipogenic differentiation of rabbit bone marrow mesenchymal stem cells (BMSCs). Primary BMSCs were isolated from rabbit bone marrow, cultured, and the markers of BMSCs on cell’s surface were analyzed using flow cytometry. The experiment involved five groups, namely, control: untreated BMSCs; model: BMSCs treated with ethanol; empty siRNA: BMSCs treated with ethanol + empty siRNA; PPARγ: BMSCs treated with ethanol + PPARγ siRNA; and PPARγ inhibitor: BMSCs treated with ethanol + T0070907. RT-PCR and Western blotting were used to detect changes in the expression level of PPARγ, PETALA2 (AP2), lipoprotein lipase (LPL), fatty acid transport protein (FATP) 1, and fatty acid transporter (FAT). Adipocyte count and triacylglycerol content of the model and the empty siRNA groups were considerably greater than the control group ( P < 0.01 ). After the inhibition with PPARγ or T0070907, adipocyte count and triacylglycerol content of the PPARγ and T0070907 groups were significantly reduced ( P < 0.01 ), with no statistically significantly difference than the control group ( P > 0.05 ). The expression levels of PPARγ gene and protein in the model and empty siRNA groups were ominously enhanced than the control group ( P < 0.01 ), and after inhibition with PPARγ or T0070907, the PPARγ gene or protein expression level of PPARγ and T0070907 groups significantly reduced ( P < 0.01 ), with no statistically significance difference compared to the control group ( P > 0.05 ). The expression levels of Ap2, LPL, FATP1, and FAT genes in the model and empty siRNA groups were considerably greater compared to the control group ( P < 0.01 ). Inhibition with PPARγ or T0070907 in the PPARγ and T0070907 groups, respectively, lead to significantly reduced expression levels of adipogenic genes ( P < 0.01 ), with no statistically significance difference compared to the control ( P > 0.05 ). Inhibition of PPARγ gene downregulates the differentiation of BMSCs into adipocytes, indicating its putative role in the expression of adipogenic genes.

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