The Experts below are selected from a list of 297 Experts worldwide ranked by ideXlab platform
Jianxin Li - One of the best experts on this subject based on the ideXlab platform.
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Fatty Acid Oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C
Stem Cell Research & Therapy, 2018Co-Authors: Zhaoyu Lin, Peiliang Shi, Anying Song, Dayuan Zou, Zan Huang, Qin Chen, Jianxin Li, Fei Liu, Xiang GaoAbstract:BackgroundChanges in metabolic pathway preferences are key events in the reprogramming process of somatic cells to induced pluripotent stem cells (iPSCs). The optimization of metabolic conditions can enhance reprogramming; however, the detailed underlying mechanisms are largely unclear. By comparing the gene expression profiles of somatic cells, intermediate-phase cells, and iPSCs, we found that carnitine palmitoyltransferase (Cpt)1b, a rate-limiting enzyme in Fatty Acid Oxidation, was significantly upregulated in the early stage of the reprogramming process.MethodsMouse embryonic fibroblasts isolated from transgenic mice carrying doxycycline (Dox)-inducible Yamanaka factor constructs were used for reprogramming. Various Fatty Acid Oxidation-related metabolites were added during the reprogramming process. Colony counting and fluorescence-activated cell sorting (FACS) were used to calculate reprogramming efficiency. Fatty Acid Oxidation-related metabolites were measured by liquid chromatography–mass spectrometry. Seahorse was used to measure the level of oxidative phosphorylation.ResultsWe found that overexpression of cpt1b enhanced reprogramming efficiency. Furthermore, palmitoylcarnitine or acetyl-CoA, the primary and final products of Cpt1-mediated Fatty Acid Oxidation, also promoted reprogramming. In the early reprogramming process, Fatty Acid Oxidation upregulated oxidative phosphorylation and downregulated protein kinase C activity. Inhibition of protein kinase C also promoted reprogramming.ConclusionWe demonstrated that Fatty Acid Oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C activity in the early stage of the reprogramming process. This study reveals that Fatty Acid Oxidation is crucial for the reprogramming efficiency.
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Fatty Acid Oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase c
Stem Cell Research & Therapy, 2018Co-Authors: Anying Song, Zan Huang, Qin Chen, Jianxin LiAbstract:Changes in metabolic pathway preferences are key events in the reprogramming process of somatic cells to induced pluripotent stem cells (iPSCs). The optimization of metabolic conditions can enhance reprogramming; however, the detailed underlying mechanisms are largely unclear. By comparing the gene expression profiles of somatic cells, intermediate-phase cells, and iPSCs, we found that carnitine palmitoyltransferase (Cpt)1b, a rate-limiting enzyme in Fatty Acid Oxidation, was significantly upregulated in the early stage of the reprogramming process. Mouse embryonic fibroblasts isolated from transgenic mice carrying doxycycline (Dox)-inducible Yamanaka factor constructs were used for reprogramming. Various Fatty Acid Oxidation-related metabolites were added during the reprogramming process. Colony counting and fluorescence-activated cell sorting (FACS) were used to calculate reprogramming efficiency. Fatty Acid Oxidation-related metabolites were measured by liquid chromatography–mass spectrometry. Seahorse was used to measure the level of oxidative phosphorylation. We found that overexpression of cpt1b enhanced reprogramming efficiency. Furthermore, palmitoylcarnitine or acetyl-CoA, the primary and final products of Cpt1-mediated Fatty Acid Oxidation, also promoted reprogramming. In the early reprogramming process, Fatty Acid Oxidation upregulated oxidative phosphorylation and downregulated protein kinase C activity. Inhibition of protein kinase C also promoted reprogramming. We demonstrated that Fatty Acid Oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C activity in the early stage of the reprogramming process. This study reveals that Fatty Acid Oxidation is crucial for the reprogramming efficiency.
Ute Spiekerkoetter - One of the best experts on this subject based on the ideXlab platform.
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Mitochondrial Fatty Acid Oxidation Disorders
Physician's Guide to the Diagnosis Treatment and Follow-Up of Inherited Metabolic Diseases, 2013Co-Authors: Ute Spiekerkoetter, M. DuranAbstract:Mitochondrial Fatty Acid Oxidation disorders have been included in newborn screening programs worldwide since the implementation of tandem mass spectrometry-based screening. Disease-specific acylcarnitine profiles pinpoint at the respective enzyme defect; however, the diagnosis has invariably to be confirmed by enzyme assay and/or molecular analysis. Metabolic profiles can be normal in the anabolic state and, consequently, newborn screening may miss the diagnosis when performed outside the catabolic state on days 2 and 3 of life. Mitochondrial Fatty Acid Oxidation disorders comprise four groups: (1) disorders of the entry of long-chain Fatty Acids into mitochondria, (2) intramitochondrial β-Oxidation defects of long-chain Fatty Acids affecting membrane-bound enzymes, (3) β-Oxidation defects of short- and medium-chain Fatty Acids affecting enzymes of the mitochondrial matrix, and (4) disorders of impaired electron transfer to the respiratory chain from mitochondrial β-Oxidation. The main pathogenic mechanisms of Fatty Acid Oxidation defects include toxic effects by accumulating acylcarnitine and acyl-CoA species and energy deficiency due to impaired Fatty Acid Oxidation and ketone body formation. The respective disorders present with heterogeneous phenotypes. Before newborn screening (NBS) was introduced, the most common clinical presentations were hypoketotic hypoglycemia and sudden death, usually precipitated by an infection or fasting in the neonatal period or early childhood. In addition, severe cardiomyopathy and arrhythmias were leading clinical signs in the first months of life. Older children or adults may present with exercise- or illness-induced rhabdomyolysis. Patients can remain asymptomatic throughout life if they have mild defects and are not exposed to metabolic stress. Correlation of genotype and/or residual enzyme activity with disease phenotype has been reported for some defects, whereas in others additional disease modifiers are suspected. With newborn screening, disease incidence has significantly increased and the proportion of milder phenotypes has grown. Newborn screening greatly reduces the morbidity and mortality, though it does not eliminate early neonatal death in severe phenotypes. With respect to the heterogeneous clinical presentation, treatment needs to be tailored to the severity of the respective phenotype and the specific disorder.
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Mitochondrial Fatty Acid Oxidation disorders: pathophysiological studies in mouse models
Journal of Inherited Metabolic Disease, 2010Co-Authors: Ute Spiekerkoetter, Philip A. WoodAbstract:Mouse models have been designed for a number of Fatty Acid Oxidation defects. Studies in these mouse models have demonstrated that different pathogenetic mechanisms play a role in the pathophysiology of defects of Fatty Acid Oxidation. Supplementation with L-carnitine does not prevent low tissue carnitine levels and induces acylcarnitine production having potentially toxic effects, as presented in very-long-chain acyl-CoA dehydrogenase (VLCAD)-deficient mice. Energy deficiency appears to be an important mechanism in the development of cardiomyopathy and skeletal myopathy in Fatty Acid Oxidation defects and is also the underlying mechanism of cold intolerance. Hypoglycemia as one major clinical sign in all Fatty Acid Oxidation defects occurs due to a reduced hepatic glucose output and an enhanced peripheral glucose uptake rather than to transcriptional changes that are also observed simultaneously, as presented in medium-chain acyl-CoA dehydrogenase (MCAD)-deficient mice. There are reports that an impaired Fatty Acid Oxidation also plays a role in intrauterine life. The embryonic loss demonstrated for some enzyme defects in the mouse supports this hypothesis. However, the exact mechanisms are unknown. This observation correlates to maternal hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, as observed in pregnancies carrying a long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD)-deficient fetus. Synergistic heterozygosity has been shown in isolated patients and in mouse models to be associated with clinical phenotypes common to Fatty Acid Oxidation disorders. Synergistic mutations may also modulate severity of the clinical phenotype and explain in part clinical heterogeneity of Fatty Acid Oxidation defects. In summary, knowledge about the different pathogenetic mechanisms and the resulting pathophysiology allows the development of specific new therapies.
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Mitochondrial Fatty Acid Oxidation disorders: clinical presentation of long-chain Fatty Acid Oxidation defects before and after newborn screening
Journal of Inherited Metabolic Disease, 2010Co-Authors: Ute SpiekerkoetterAbstract:The different long-chain Fatty Acid Oxidation defects present with similar heterogeneous clinical phenotypes of different severity. Organs mainly affected comprise the heart, liver, and skeletal muscles. All symptoms are reversible with sufficient energy supply. In some long-chain Fatty Acid Oxidation defects, disease-specific symptoms occur. Only in disorders of the mitochondrial trifunctional protein (TFP) complex, including long-chain 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase (LCHAD) deficiency, neuropathy and retinopathy develop that are progressive and irreversible despite current treatment measures. In most long-chain Fatty Acid Oxidation defects, no clear genotype-phenotype correlation exists due to molecular heterogeneity. However, some isolated mutations have been identified to be associated with only mild phenotypes, e.g., the V243A mutation in very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. LCHAD deficiency is due to the prevalent homozygous 1528G>C mutation and presents with heterogeneous clinical phenotypes, suggesting the importance of other environmental and genetic factors. For some disorders, it was shown that residual enzyme activity measured in fibroblasts or lymphocytes correlated with severity of clinical phenotype. Implementation of newborn screening has significantly reduced morbidity and mortality of long-chain Fatty Acid Oxidation defects. However, the severest forms of TFP deficiency are still highly associated with neonatal death. Newborn screening also identifies a great number of mildly affected patients who may never develop clinical symptoms throughout life. However, later-onset exercise-induced myopathic symptoms remain characteristic clinical features of long-chain Fatty Acid Oxidation defects. Disease prevalence has increased with newborn screening.
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treatment recommendations in long chain Fatty Acid Oxidation defects consensus from a workshop
Journal of Inherited Metabolic Disease, 2009Co-Authors: Ute Spiekerkoetter, Martin Lindner, Rene Santer, M Grotzke, Matthias R Baumgartner, H Boehles, A Das, C Haase, Julia B Hennermann, D KarallAbstract:Published data on treatment of Fatty Acid Oxidation defects are scarce. Treatment recommendations have been developed on the basis of observations in 75 patients with long-chain Fatty Acid Oxidation defects from 18 metabolic centres in Central Europe. Recommendations are based on expert practice and are suggested to be the basis for further multicentre prospective studies and the development of approved treatment guidelines. Considering that disease complications and prognosis differ between different disorders of long-chain Fatty Acid Oxidation and also depend on the severity of the underlying enzyme deficiency, treatment recommendations have to be disease-specific and depend on individual disease severity. Disorders of the mitochondrial trifunctional protein are associated with the most severe clinical picture and require a strict fat-reduced and fat-modified (medium-chain triglyceride-supplemented) diet. Many patients still suffer acute life-threatening events or long-term neuropathic symptoms despite adequate treatment, and newborn screening has not significantly changed the prognosis for these severe phenotypes. Very long-chain acyl-CoA dehydrogenase deficiency recognized in neonatal screening, in contrast, frequently has a less severe disease course and dietary restrictions in many patients may be loosened. On the basis of the collected data, recommendations are given with regard to the fat and carbohydrate content of the diet, the maximal length of fasting periods and the use of l-carnitine in long-chain Fatty Acid Oxidation defects.
Anying Song - One of the best experts on this subject based on the ideXlab platform.
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Fatty Acid Oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C
Stem Cell Research & Therapy, 2018Co-Authors: Zhaoyu Lin, Peiliang Shi, Anying Song, Dayuan Zou, Zan Huang, Qin Chen, Jianxin Li, Fei Liu, Xiang GaoAbstract:BackgroundChanges in metabolic pathway preferences are key events in the reprogramming process of somatic cells to induced pluripotent stem cells (iPSCs). The optimization of metabolic conditions can enhance reprogramming; however, the detailed underlying mechanisms are largely unclear. By comparing the gene expression profiles of somatic cells, intermediate-phase cells, and iPSCs, we found that carnitine palmitoyltransferase (Cpt)1b, a rate-limiting enzyme in Fatty Acid Oxidation, was significantly upregulated in the early stage of the reprogramming process.MethodsMouse embryonic fibroblasts isolated from transgenic mice carrying doxycycline (Dox)-inducible Yamanaka factor constructs were used for reprogramming. Various Fatty Acid Oxidation-related metabolites were added during the reprogramming process. Colony counting and fluorescence-activated cell sorting (FACS) were used to calculate reprogramming efficiency. Fatty Acid Oxidation-related metabolites were measured by liquid chromatography–mass spectrometry. Seahorse was used to measure the level of oxidative phosphorylation.ResultsWe found that overexpression of cpt1b enhanced reprogramming efficiency. Furthermore, palmitoylcarnitine or acetyl-CoA, the primary and final products of Cpt1-mediated Fatty Acid Oxidation, also promoted reprogramming. In the early reprogramming process, Fatty Acid Oxidation upregulated oxidative phosphorylation and downregulated protein kinase C activity. Inhibition of protein kinase C also promoted reprogramming.ConclusionWe demonstrated that Fatty Acid Oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C activity in the early stage of the reprogramming process. This study reveals that Fatty Acid Oxidation is crucial for the reprogramming efficiency.
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Fatty Acid Oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase c
Stem Cell Research & Therapy, 2018Co-Authors: Anying Song, Zan Huang, Qin Chen, Jianxin LiAbstract:Changes in metabolic pathway preferences are key events in the reprogramming process of somatic cells to induced pluripotent stem cells (iPSCs). The optimization of metabolic conditions can enhance reprogramming; however, the detailed underlying mechanisms are largely unclear. By comparing the gene expression profiles of somatic cells, intermediate-phase cells, and iPSCs, we found that carnitine palmitoyltransferase (Cpt)1b, a rate-limiting enzyme in Fatty Acid Oxidation, was significantly upregulated in the early stage of the reprogramming process. Mouse embryonic fibroblasts isolated from transgenic mice carrying doxycycline (Dox)-inducible Yamanaka factor constructs were used for reprogramming. Various Fatty Acid Oxidation-related metabolites were added during the reprogramming process. Colony counting and fluorescence-activated cell sorting (FACS) were used to calculate reprogramming efficiency. Fatty Acid Oxidation-related metabolites were measured by liquid chromatography–mass spectrometry. Seahorse was used to measure the level of oxidative phosphorylation. We found that overexpression of cpt1b enhanced reprogramming efficiency. Furthermore, palmitoylcarnitine or acetyl-CoA, the primary and final products of Cpt1-mediated Fatty Acid Oxidation, also promoted reprogramming. In the early reprogramming process, Fatty Acid Oxidation upregulated oxidative phosphorylation and downregulated protein kinase C activity. Inhibition of protein kinase C also promoted reprogramming. We demonstrated that Fatty Acid Oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C activity in the early stage of the reprogramming process. This study reveals that Fatty Acid Oxidation is crucial for the reprogramming efficiency.
Xiang Gao - One of the best experts on this subject based on the ideXlab platform.
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Fatty Acid Oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C
Stem Cell Research & Therapy, 2018Co-Authors: Zhaoyu Lin, Peiliang Shi, Anying Song, Dayuan Zou, Zan Huang, Qin Chen, Jianxin Li, Fei Liu, Xiang GaoAbstract:BackgroundChanges in metabolic pathway preferences are key events in the reprogramming process of somatic cells to induced pluripotent stem cells (iPSCs). The optimization of metabolic conditions can enhance reprogramming; however, the detailed underlying mechanisms are largely unclear. By comparing the gene expression profiles of somatic cells, intermediate-phase cells, and iPSCs, we found that carnitine palmitoyltransferase (Cpt)1b, a rate-limiting enzyme in Fatty Acid Oxidation, was significantly upregulated in the early stage of the reprogramming process.MethodsMouse embryonic fibroblasts isolated from transgenic mice carrying doxycycline (Dox)-inducible Yamanaka factor constructs were used for reprogramming. Various Fatty Acid Oxidation-related metabolites were added during the reprogramming process. Colony counting and fluorescence-activated cell sorting (FACS) were used to calculate reprogramming efficiency. Fatty Acid Oxidation-related metabolites were measured by liquid chromatography–mass spectrometry. Seahorse was used to measure the level of oxidative phosphorylation.ResultsWe found that overexpression of cpt1b enhanced reprogramming efficiency. Furthermore, palmitoylcarnitine or acetyl-CoA, the primary and final products of Cpt1-mediated Fatty Acid Oxidation, also promoted reprogramming. In the early reprogramming process, Fatty Acid Oxidation upregulated oxidative phosphorylation and downregulated protein kinase C activity. Inhibition of protein kinase C also promoted reprogramming.ConclusionWe demonstrated that Fatty Acid Oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C activity in the early stage of the reprogramming process. This study reveals that Fatty Acid Oxidation is crucial for the reprogramming efficiency.
Zan Huang - One of the best experts on this subject based on the ideXlab platform.
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Fatty Acid Oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C
Stem Cell Research & Therapy, 2018Co-Authors: Zhaoyu Lin, Peiliang Shi, Anying Song, Dayuan Zou, Zan Huang, Qin Chen, Jianxin Li, Fei Liu, Xiang GaoAbstract:BackgroundChanges in metabolic pathway preferences are key events in the reprogramming process of somatic cells to induced pluripotent stem cells (iPSCs). The optimization of metabolic conditions can enhance reprogramming; however, the detailed underlying mechanisms are largely unclear. By comparing the gene expression profiles of somatic cells, intermediate-phase cells, and iPSCs, we found that carnitine palmitoyltransferase (Cpt)1b, a rate-limiting enzyme in Fatty Acid Oxidation, was significantly upregulated in the early stage of the reprogramming process.MethodsMouse embryonic fibroblasts isolated from transgenic mice carrying doxycycline (Dox)-inducible Yamanaka factor constructs were used for reprogramming. Various Fatty Acid Oxidation-related metabolites were added during the reprogramming process. Colony counting and fluorescence-activated cell sorting (FACS) were used to calculate reprogramming efficiency. Fatty Acid Oxidation-related metabolites were measured by liquid chromatography–mass spectrometry. Seahorse was used to measure the level of oxidative phosphorylation.ResultsWe found that overexpression of cpt1b enhanced reprogramming efficiency. Furthermore, palmitoylcarnitine or acetyl-CoA, the primary and final products of Cpt1-mediated Fatty Acid Oxidation, also promoted reprogramming. In the early reprogramming process, Fatty Acid Oxidation upregulated oxidative phosphorylation and downregulated protein kinase C activity. Inhibition of protein kinase C also promoted reprogramming.ConclusionWe demonstrated that Fatty Acid Oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C activity in the early stage of the reprogramming process. This study reveals that Fatty Acid Oxidation is crucial for the reprogramming efficiency.
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Fatty Acid Oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase c
Stem Cell Research & Therapy, 2018Co-Authors: Anying Song, Zan Huang, Qin Chen, Jianxin LiAbstract:Changes in metabolic pathway preferences are key events in the reprogramming process of somatic cells to induced pluripotent stem cells (iPSCs). The optimization of metabolic conditions can enhance reprogramming; however, the detailed underlying mechanisms are largely unclear. By comparing the gene expression profiles of somatic cells, intermediate-phase cells, and iPSCs, we found that carnitine palmitoyltransferase (Cpt)1b, a rate-limiting enzyme in Fatty Acid Oxidation, was significantly upregulated in the early stage of the reprogramming process. Mouse embryonic fibroblasts isolated from transgenic mice carrying doxycycline (Dox)-inducible Yamanaka factor constructs were used for reprogramming. Various Fatty Acid Oxidation-related metabolites were added during the reprogramming process. Colony counting and fluorescence-activated cell sorting (FACS) were used to calculate reprogramming efficiency. Fatty Acid Oxidation-related metabolites were measured by liquid chromatography–mass spectrometry. Seahorse was used to measure the level of oxidative phosphorylation. We found that overexpression of cpt1b enhanced reprogramming efficiency. Furthermore, palmitoylcarnitine or acetyl-CoA, the primary and final products of Cpt1-mediated Fatty Acid Oxidation, also promoted reprogramming. In the early reprogramming process, Fatty Acid Oxidation upregulated oxidative phosphorylation and downregulated protein kinase C activity. Inhibition of protein kinase C also promoted reprogramming. We demonstrated that Fatty Acid Oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C activity in the early stage of the reprogramming process. This study reveals that Fatty Acid Oxidation is crucial for the reprogramming efficiency.
