scholarly journals ANGPTL4 supports glutamine metabolism and promotes fatty acid oxidation in nonsmall cell lung cancer cells

2020 ◽  
Author(s):  
Song Xiao ◽  
Wang Nai-Dong ◽  
Jin-Xiang Yan ◽  
Long Tian ◽  
Xiu-Rong Lu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Fatty Acid ◽  
Energy Metabolism ◽  
Fatty Acid Oxidation ◽  
Metabolic Diseases ◽  
Nonsmall Cell Lung Cancer ◽  
Glutamine Metabolism ◽  
Acid Oxidation ◽  
Glutamine Consumption ◽  
Glutamine Deprivation

Abstract Background Angiopoietin-like proteins (ANGPTLs) 4 is key factor in the regulation of lipid and glucose metabolism in metabolic diseases. It also has been demonstrated highly expressed in cancers, but the regulation of energy metabolism on tumor remains to be determined.Methods Two different NSCLC cells A549 and H1299 were used to investigate the role of ANGPTLs 4 in energy metabolism by tracer technique and seahorse XF technology in ANGPTLs4 knockdown cell. RNA microarray and specific inhibitors were used in identification targets in overexpression ANGPTLs4 cells.Results Knockdown ANGPTLs4 could inhibit the energy metabolism and proliferation of NSCLC cells. Knockdown ANGPTLs4 had no significant effect on glycolysis, but affected the glutamine consumption and fatty acid oxidation. Knockdown ANGPTLs4 also significantly inhibited the growth of metastasis and energy metabolism of tumor in mice, but had a weak effect on glycolysis. RNA microarray analysis showed that ANGPTLs4 significantly affected GLS and CPT1. ANGPTLs4 overexpression cells exposed to glutamine deprivation, the effect on cell proliferation and energy metabolism were significantly decreased, but still has difference compared with normal NSCLC cells. ANGPTLs4 overexpression cells treated with GLS and CPT1 inhibitor at the same time, the regulatory effects on cell proliferation and energy metabolism were disappeared.Conclusions ANGPTLs4 could promote the glutamine consumption and fatty acid oxidation, but not glycolysis, and accelerated the energy metabolism in NSCLC.

Leptin promotes fatty acid oxidation and OXPHOS via the c-Myc/PGC-1 pathway in cancer cells

2019 ◽  
Vol 51 (7) ◽  
pp. 707-714 ◽  
Author(s):  
Qianqian Liu ◽  
Yang Sun ◽  
Zaiyi Fei ◽  
Zhibin Yang ◽  
Ke Duan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Fatty Acid ◽  
Energy Metabolism ◽  
Tumor Cells ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Nadh:Ubiquinone Oxidoreductase ◽  
Expression Levels ◽  
Hct116 Cells ◽  
Mcf 7

Abstract Alteration in cellular energy metabolism plays a critical role in the development and progression of cancer. Leptin is a hormone secreted by adipose tissue. Recent reports have shown that leptin can induce cancer cell proliferation and regulate cell energy metabolism, but the regulatory mechanism is still unclear. Here, we showed that leptin could promote cell proliferation and maintain high adenosine triphosphate levels in HCT116 and MCF-7 cells. The expression levels of carnitine palmitoyl transferase 1A (CPT1A), pyruvate dehydrogenase, succinate dehydrogenase subunit A and mitochondrial respiratory chain-associated proteins NADH dehydrogenase 1 (ND1), NADH:ubiquinone oxidoreductase subunit B8, and mitochondrial transcription factor A (TFAM) were distinctly increased in leptin-treated HCT116 and MCF-7 cells, while fatty acid synthase and lactate dehydrogenase expression were downregulated. Simultaneously, we found that c-Myc and peroxisome proliferator-activated receptor gamma co-activator 1 (PGC-1) protein expression levels were significantly increased. These results indicated that leptin boosted fatty acid β-oxidation and the tricarboxylic acid cycle, enhanced oxidative phosphorylation (OXPHOS) activity, and inhibited fatty acid synthesis and glycolysis in tumor cells. Gene transfection experiments revealed that leptin could induce the expression of c-Myc. Moreover, the expressions of PGC-1, CPT1A, and TFAM proteins were downregulated in HCT116 cells with low expression of c-Myc, and the expression levels of these proteins were increased in HCT116 cells overexpressing c-Myc. These findings suggest that leptin plays an important role in the regulation of energy metabolism in tumor cells. It may regulate fatty acid oxidation and OXPHOS of tumor cells by regulating the c-Myc/PGC-1 pathway. Targeting metabolic pathways for cancer treatment has been investigated as potential preventive or therapeutic methods. This study has important implications for the clinical therapy of tumor cell metabolism through hormone regulation.

scholarly journals Acetylation and succinylation contribute to maturational alterations in energy metabolism in the newborn heart

2016 ◽  
Vol 311 (2) ◽  
pp. H347-H363 ◽  
Author(s):  
Arata Fukushima ◽  
Osama Abo Alrob ◽  
Liyan Zhang ◽  
Cory S. Wagg ◽  
Tariq Altamimi ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Energy Metabolism ◽  
Fatty Acid Oxidation ◽  
Glucose Oxidation ◽  
Acid Oxidation ◽  
Amino Acid Synthesis ◽  
Oxidation Rates ◽  
Cardiac Energy Metabolism ◽  
Cardiac Energy ◽  
The Impact

Dramatic maturational changes in cardiac energy metabolism occur in the newborn period, with a shift from glycolysis to fatty acid oxidation. Acetylation and succinylation of lysyl residues are novel posttranslational modifications involved in the control of cardiac energy metabolism. We investigated the impact of changes in protein acetylation/succinylation on the maturational changes in energy metabolism of 1-, 7-, and 21-day-old rabbit hearts. Cardiac fatty acid β-oxidation rates increased in 21-day vs. 1- and 7-day-old hearts, whereas glycolysis and glucose oxidation rates decreased in 21-day-old hearts. The fatty acid oxidation enzymes, long-chain acyl-CoA dehydrogenase (LCAD) and β-hydroxyacyl-CoA dehydrogenase (β-HAD), were hyperacetylated with maturation, positively correlated with their activities and fatty acid β-oxidation rates. This alteration was associated with increased expression of the mitochondrial acetyltransferase, general control of amino acid synthesis 5 like 1 (GCN5L1), since silencing GCN5L1 mRNA in H9c2 cells significantly reduced acetylation and activity of LCAD and β-HAD. An increase in mitochondrial ATP production rates with maturation was associated with the decreased acetylation of peroxisome proliferator-activated receptor-γ coactivator-1α, a transcriptional regulator for mitochondrial biogenesis. In addition, hypoxia-inducible factor-1α, hexokinase, and phosphoglycerate mutase expression declined postbirth, whereas acetylation of these glycolytic enzymes increased. Phosphorylation rather than acetylation of pyruvate dehydrogenase (PDH) increased in 21-day-old hearts, accounting for the low glucose oxidation postbirth. A maturational increase was also observed in succinylation of PDH and LCAD. Collectively, our data are the first suggesting that acetylation and succinylation of the key metabolic enzymes in newborn hearts play a crucial role in cardiac energy metabolism with maturation. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/acetylation-control-of-energy-metabolism-in-newborn-hearts/ .

scholarly journals The role of tandem mass spectrometry in the diagnosis of inherited metabolic diseases

2018 ◽  
Vol 5 (3) ◽  
pp. 96-105 ◽  
Author(s):  
G. V. Baydakova ◽  
T. A. Ivanova ◽  
E. Yu. Zakharova ◽  
O. S. Kokorina
Keyword(s):  
Mass Spectrometry ◽  
Fatty Acid ◽  
Tandem Mass Spectrometry ◽  
Fatty Acid Oxidation ◽  
Metabolic Diseases ◽  
Acid Oxidation ◽  
Tandem Mass ◽  
Organic Acidurias ◽  
Inherited Metabolic Diseases ◽  
Screening Programs

This paper reviews the clinical applications of tandem mass spectrometry in diagnosis and screening for inherited metabolic diseases. The broad-spectrum of diseases covered, specificity, ease of sample preparation, and high throughput provided by the MS/MS technology has led to the development of multi-disorder newborn screening programs in many countries for amino acid disorders, organic acidurias, and fatty acid oxidation defects. The application of MS/MS in selective screening has revolutionized the field and made a major impact on the detection of certain disease classes such as the fatty acid oxidation defects. New specific and rapid tandem mass spectrometry (MS/MS) and high performance liquid chromatography–MS/MS methods are supplementing or replacing some of the classical gas chromatography– MS/MS methods for a multitude of metabolites and disorders. In the near future, we should expect the emergence of new promising methods for diagnosing not only individual nosologic forms, but also entire groups of inherited metabolic diseases.

scholarly journals Reduced Liver-Specific PGC1a Increases Susceptibility for Short-Term Diet-induced Weight Gain in Male Mice

2020 ◽  
Author(s):  
E. Matthew Morris ◽  
Roberto D. Noland ◽  
Michael E. Ponte ◽  
Michelle L. Montonye ◽  
Julie A. Christianson ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Weight Gain ◽  
Energy Metabolism ◽  
Energy Balance ◽  
Fatty Acid Oxidation ◽  
Positive Energy ◽  
Acid Oxidation ◽  
Male Mice ◽  
Short Term

AbstractCentral integration of peripheral neural signals is one mechanism by which systemic energy homeostasis is regulated. Previous work described increased acute food intake following chemical reduction of hepatic fatty acid oxidation and ATP levels, which was prevented by common hepatic branch vagotomy (HBV). However, possible offsite actions of the chemical compounds confound the precise role of liver energy metabolism. Herein, we used a liver-specific PGC1a heterozygous (LPGC1a) mouse model, with associated reductions in mitochondrial fatty acid oxidation and respiratory capacity, to assess the role of liver energy metabolism in systemic energy homeostasis. LPGC1a male mice have 70% greater high-fat/high-sucrose (HFHS) diet-induced weight gain and 35% greater positive energy balance compared to wildtype (WT) (p<0.05). The greater energy balance was associated with altered feeding behavior and lower activity energy expenditure during HFHS in LPGC1a males. Importantly, no differences in HFHS-induced weight gain or energy metabolism was observed between female WT and LPGC1a mice. WT and LPGC1a mice underwent sham or HBV to assess whether vagal signaling was involved in HFHS-induced weight gain of male LPGC1a mice. HBV increased HFHS-induced weight gain (85%, p<0.05) in male WT, but not LPGC1a mice. As above, sham LPGC1a males gain 70% more weight during short-term HFHS feeding than sham WT (p<0.05). These data demonstrate a sexspecific role of reduced liver energy metabolism in acute diet-induced weight gain, and the need of more nuanced assessment of the role of vagal signaling in short-term diet-induced weight gain.Key Points SummaryReduced liver PGC1a expression results in reduced mitochondrial fatty acid oxidation and respiratory capacity in male mice.Male mice with reduced liver PGC1a expression (LPGC1a) demonstrate greater short-term high-fat/high-sucrose diet-induced weight gain compared to wildtype.Greater positive energy balance during HFHS feeding in male LPGC1a mice is associated with altered food intake patterns and reduced activity energy expenditure.Female LPGC1a mice do not have differences in short-term HFHS-induced body weight gain or energy metabolism compared to wildtype.Disruption of vagal signaling through common hepatic branch vagotomy increases short-term HFHS-induced weight gain in male wildtype mice, but does not alter male LPGC1a weight gain.

Abstract 15649: Pharmacological Inhibition of Aldose Reductase by AT001 Prevents Abnormal Cardiac Energy Metabolism and Improves Heart Function in an Animal Model of Diabetic Cardiomyopathy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Keshav Gopal ◽  
Qutuba Karwi ◽  
Seyed Amirhossein Tabatabaei Dakhili ◽  
Riccardo Perfetti ◽  
Ravichandran Ramasamy ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Energy Metabolism ◽  
Fatty Acid Oxidation ◽  
Diabetic Cardiomyopathy ◽  
Acid Oxidation ◽  
Cardiac Energetics ◽  
Cardiac Efficiency ◽  
Oxidation Rates ◽  
Cardiac Energy Metabolism ◽  
Cardiac Energy

Introduction: Diabetic Cardiomyopathy (DCM) is a major cause of death in people with type 2 diabetes (T2D). Alterations in cardiac energy metabolism including increased fatty acid oxidation rates and reduced glucose oxidation rates are key contributing factors to the development of DCM. Studies have shown that Aldose Reductase (AR), an enzyme activated under hyperglycemic conditions, can modulate myocardial glucose and fatty acid oxidation, and promotes cardiac dysfunction. Hypothesis: Pharmacological inhibition of AR using a next-generation inhibitor AT-001, can mitigate DCM in mice by modulating cardiac energy metabolism and improving cardiac efficiency. Methods: Male human AR overexpressing (hAR-Tg) and C57BL/6J (Control) mice were subjected to experimental T2D (high-fat diet [60% kcal from lard] for 10-wk with a single intraperitoneal streptozotocin injection of 75 mg/kg) and treated for the last 3-wk with AT-001 (40mg/kg/day) or vehicle via oral gavage. Cardiac energy metabolism and in vivo cardiac function were assessed via isolated working heart perfusions and ultrasound echocardiography, respectively. Results: AT-001 treatment significantly improved cardiac energetics in a murine model of DCM (hAR-Tg mice with T2D). Particularly, AT-001-treated mice exhibited decreased cardiac fatty acid oxidation rates compared to the vehicle-treated mice (342 ± 53 vs 964 ± 130 nmol/min/g dry wt.). Concurrently, there was a significant decrease in cardiac oxygen consumption in the AT-001-treated compared to the vehicle-treated mice (41 ± 12 vs 60 ± 11 μmol/min/g dry wt.), suggesting increased cardiac efficiency. Furthermore, treatment with AT-001 prevented cardiac structural and functional abnormalities present in DCM, including diastolic dysfunction as reflected by an increase in the tissue Doppler E’/A’ ratio and decrease in E/E’ ratio. Moreover, AT-001 treatment prevented cardiac hypertrophy as reflected by a decrease in LV mass in AT-001-treated mice. Conclusions: AR inhibition with AT-001 prevents cardiac structural and functional abnormalities in a mouse model of DCM, and normalizes cardiac energetics by shifting cardiac metabolism towards a non-diabetic metabolic state.

3,5-Diiodo-l-thyronine rapidly enhances mitochondrial fatty acid oxidation rate and thermogenesis in rat skeletal muscle: AMP-activated protein kinase involvement

2009 ◽  
Vol 296 (3) ◽  
pp. E497-E502 ◽  
Author(s):  
A. Lombardi ◽  
P. de Lange ◽  
E. Silvestri ◽  
R. A. Busiello ◽  
A. Lanni ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Energy Metabolism ◽  
Fatty Acid Oxidation ◽  
Atp Synthesis ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Amp Activated Protein Kinase

Triiodothyronine regulates energy metabolism and thermogenesis. Among triiodothyronine derivatives, 3,5-diiodo-l-thyronine (T2) has been shown to exert marked effects on energy metabolism by acting mainly at the mitochondrial level. Here we investigated the capacity of T2 to affect both skeletal muscle mitochondrial substrate oxidation and thermogenesis within 1 h after its injection into hypothyroid rats. Administration of T2 induced an increase in mitochondrial oxidation when palmitoyl-CoA (+104%), palmitoylcarnitine (+80%), or succinate (+30%) was used as substrate, but it had no effect when pyruvate was used. T2 was able to 1) activate the AMPK-ACC-malonyl-CoA metabolic signaling pathway known to direct lipid partitioning toward oxidation and 2) increase the importing of fatty acids into the mitochondrion. These results suggest that T2 stimulates mitochondrial fatty acid oxidation by activating several metabolic pathways, such as the fatty acid import/β-oxidation cycle/FADH2-linked respiratory pathways, where fatty acids are imported. T2 also enhanced skeletal muscle mitochondrial thermogenesis by activating pathways involved in the dissipation of the proton-motive force not associated with ATP synthesis (“proton leak”), the effect being dependent on the presence of free fatty acids inside mitochondria. We conclude that skeletal muscle is a target for T2, and we propose that, by activating processes able to enhance mitochondrial fatty acid oxidation and thermogenesis, T2 could play a role in protecting skeletal muscle against excessive intramyocellular lipid storage, possibly allowing it to avoid functional disorders.

scholarly journals Reduced Liver-Specific PGC1a Increases Susceptibility for Short-Term Diet-Induced Weight Gain in Male Mice

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2596
Author(s):  
E. Matthew Morris ◽  
Roberto D. Noland ◽  
Michael E. Ponte ◽  
Michelle L. Montonye ◽  
Julie A. Christianson ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Weight Gain ◽  
Energy Metabolism ◽  
Fatty Acid Oxidation ◽  
Energy Homeostasis ◽  
Chemical Reduction ◽  
Acid Oxidation ◽  
Short Term ◽  
Mitochondrial Fatty Acid

The central integration of peripheral neural signals is one mechanism by which systemic energy homeostasis is regulated. Previously, increased acute food intake following the chemical reduction of hepatic fatty acid oxidation and ATP levels was prevented by common hepatic branch vagotomy (HBV). However, possible offsite actions of the chemical compounds confound the precise role of liver energy metabolism. Herein, we used a hepatocyte PGC1a heterozygous (LPGC1a) mouse model, with associated reductions in mitochondrial fatty acid oxidation and respiratory capacity, to assess the role of liver energy metabolism in systemic energy homeostasis. LPGC1a male, but not female, mice had a 70% greater high-fat/high-sucrose (HFHS) diet-induced weight gain compared to wildtype (WT) mice (p < 0.05). The greater weight gain was associated with altered feeding behavior and lower activity energy expenditure during the HFHS diet in LPGC1a males. WT and LPGC1a mice underwent sham surgery or HBV to assess whether vagal signaling was involved in the HFHS-induced weight gain of male LPGC1a mice. HBV increased HFHS-induced weight gain (85%, p < 0.05) in male WT mice, but not LPGC1a mice. These data demonstrate a sex-specific role of reduced liver energy metabolism in acute diet-induced weight gain, and the need for a more nuanced assessment of the role of vagal signaling in short-term diet-induced weight gain.

scholarly journals Inhibition of carnitine palmitoyl transferase 1A-induced fatty acid oxidation suppresses cell progression in gastric cancer

2020 ◽  
Author(s):  
Liqiang Wang ◽  
Changfeng Li ◽  
Yumei Song ◽  
ZhenKun Yan
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Molecular Mechanisms ◽  
High Rate ◽  
Acid Oxidation ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Gastric cancer (GC) has a high rate of metastasis which thereason leading to death. Carnitine palmitoyltransferase 1a (CPT1A) has been reported to play a critical obstacle to various types of cancer progression, which is an attractive focus in anti-cancer therapy. However, the underlying molecular mechanisms of CPT1A involved in GC have not been clarified unclear. Methods: To determine the expression of CPT1A in human GC tissues and cells and illustrate whether it is correlated with the clinical pathologic characteristics and prognosis in GC patients. Its roles and potential mechanisms in regulating tumor growth and invasion were evaluated by CPT1A knockdown/overexpression of GC cells in vitro . Results: Marked upregulation of CPT1A protein expression was observed in GC cells and tissues, which was associated with grade, pathological stage, lymph node metastasis and poor prognosis in patients with GC. CPT1A overexpression also promoted the proliferation, invasion, EMT process of GC cells. In addition, CPT1A upregulation activated GC cell FAO via increasing NADP + /NADPH ratio, whereas inhibiting of FAO abolished the effects of CPT1A on GC cell proliferation and migration. Conclusion: Our results examine that CPT1A-mediated FAO activation increases GC cell proliferation and migration, supporting that CPT1A is a useful prognostic biomarker and an attractive focus for GC. Keywords: CPT1A; gastric cancer; fatty acid oxidation; prognostic; progression

scholarly journals A dietary anthocyanin cyanidin-3-O-glucoside binds to PPARs to regulate glucose metabolism and insulin sensitivity in mice

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Yaoyao Jia ◽  
Chunyan Wu ◽  
Young-Suk Kim ◽  
Seung Ok Yang ◽  
Yeonji Kim ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Energy Metabolism ◽  
Glucose Tolerance ◽  
Fatty Acid Oxidation ◽  
C2c12 Myotubes ◽  
Acid Oxidation ◽  
Metabolite Profiles ◽  
Hepatic Fatty Acid Oxidation ◽  
Fuel Preference

AbstractWe demonstrate the mechanism by which C3G, a major dietary anthocyanin, regulates energy metabolism and insulin sensitivity. Oral administration of C3G reduced hepatic and plasma triglyceride levels, adiposity, and improved glucose tolerance in mice fed high-fat diet. Hepatic metabolomic analysis revealed that C3G shifted metabolite profiles towards fatty acid oxidation and ketogenesis. C3G increased glucose uptake in HepG2 cells and C2C12 myotubes and induced the rate of hepatic fatty acid oxidation. C3G directly interacted with and activated PPARs, with the highest affinity for PPARα. The ability of C3G to reduce plasma and hepatic triglycerides, glucose tolerance, and adiposity and to induce oxygen consumption and energy expenditure was abrogated in PPARα-deficient mice, suggesting that PPARα is the major target for C3G. These findings demonstrate that the dietary anthocyanin C3G activates PPARs, a master regulators of energy metabolism. C3G is an agonistic ligand of PPARs and stimulates fuel preference to fat.

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