Effects of Different Fatty Acid Chain Lengths on Fatty Acid Oxidation-Related Protein Expression Levels in Rat Skeletal Muscles

Abstract Background Acylcarnitine is an intermediate product of fatty acid oxidation. It is reported to be closely associated with the occurrence of diabetic cardiomyopathy (DCM). However, the mechanism of acylcarnitine affecting myocardial disorders is yet to be explored. This current research explores the different chain lengths of acylcarnitines as biomarkers for the early diagnosis of DCM and the mechanism of acylcarnitines for the development of DCM in-vitro. Methods In a retrospective non-interventional study, 50 simple type 2 diabetes mellitus patients and 50 DCM patients were recruited. Plasma samples from both groups were analyzed by high throughput metabolomics and cluster heat map using mass spectrometry. Principal component analysis was used to compare the changes occurring in the studied 25 acylcarnitines. Multivariable binary logistic regression was used to analyze the odds ratio of each group for factors and the 95% confidence interval in DCM. Myristoylcarnitine (C14) exogenous intervention was given to H9c2 cells to verify the expression of lipid metabolism-related protein, inflammation-related protein expression, apoptosis-related protein expression, and cardiomyocyte hypertrophy and fibrosis-related protein expression. Results Factor 1 (C14, lauroylcarnitine, tetradecanoyldiacylcarnitine, 3-hydroxyl-tetradecanoylcarnitine, arachidic carnitine, octadecanoylcarnitine, 3-hydroxypalmitoleylcarnitine) and factor 4 (octanoylcarnitine, hexanoylcarnitine, decanoylcarnitine) were positively correlated with the risk of DCM. Exogenous C14 supplementation to cardiomyocytes led to increased lipid deposition in cardiomyocytes along with the obstacles in adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathways and affecting fatty acid oxidation. This further caused myocardial lipotoxicity, ultimately leading to cardiomyocyte hypertrophy, fibrotic remodeling, and increased apoptosis. However, this effect was mitigated by the AMPK agonist acadesine. Conclusions The increased plasma levels in medium and long-chain acylcarnitine extracted from factors 1 and 4 are closely related to the risk of DCM, indicating that these factors can be an important tool for DCM risk assessment. C14 supplementation associated lipid accumulation by inhibiting the AMPK/ACC/CPT1 signaling pathway, aggravated myocardial lipotoxicity, increased apoptosis apart from cardiomyocyte hypertrophy and fibrosis were alleviated by the acadesine.

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Mitochondrial and peroxisomal fatty acid oxidation capacities increase in the skeletal muscles of young pigs during early postnatal development but are not affected by cold stress

Reproduction Nutrition Development ◽

10.1051/rnd:2003013 ◽

2003 ◽

Vol 43 (2) ◽

pp. 155-166 ◽

Cited By ~ 6

Author(s):

Patrick Herpin ◽

Annie Vincent ◽

Martine Fillaut ◽

Bruno Piteira Bonito ◽

Jean-Fran�ois Hocquette

Keyword(s):

Fatty Acid ◽

Cold Stress ◽

Postnatal Development ◽

Fatty Acid Oxidation ◽

Skeletal Muscles ◽

Acid Oxidation ◽

Early Postnatal Development ◽

Young Pigs ◽

Peroxisomal Fatty Acid Oxidation ◽

Peroxisomal Fatty Acid

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Modulation of Cardiac Metabolism in Heart Failure

International Cardiovascular Forum Journal ◽

10.17987/icfj.v17i0.597 ◽

2019 ◽

Vol 17 ◽

Author(s):

Giuseppe Rosano ◽

Andrew Coats

Keyword(s):

Heart Failure ◽

Fatty Acid ◽

Free Fatty Acid ◽

Fatty Acid Oxidation ◽

Skeletal Muscles ◽

Cardiac Metabolism ◽

Acid Oxidation ◽

Patients With Heart Failure ◽

Free Fatty Acid Oxidation ◽

Capacity Modulation

Heart failure is associated with altered cardiac metabolism, in part, due to maladaptive mechanisms, in part secondary to comorbidities such as diabetes and ischaemic heart disease. The metabolic derangements taking place in heart failure are not limited to the cardiac myocytes, but extend to skeletal muscles and the vasculature causing changes that contribute to the worsening of exercise capacity. Modulation of cardiac metabolism with partial inhibition of free fatty acid oxidation has been shown to be beneficial in patients with heart failure. At the present, the bulk of evidence for this class of drugs comes from Trimetazidine. Newer compounds partially inhibiting free fatty acid oxidation or facilitating the electron transport on the mitochondrial cristae are in early phase of their clinical development.

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

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmz058 ◽

2019 ◽

Vol 51 (7) ◽

pp. 707-714 ◽

Cited By ~ 2

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.

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Enhanced Fatty Acid Oxidation and FATP4 Protein Expression after Endurance Exercise Training in Human Skeletal Muscle

PLoS ONE ◽

10.1371/journal.pone.0029391 ◽

2012 ◽

Vol 7 (1) ◽

pp. e29391 ◽

Cited By ~ 29

Author(s):

Jacob Jeppesen ◽

Andreas B. Jordy ◽

Kim A. Sjøberg ◽

Joachim Füllekrug ◽

Andreas Stahl ◽

...

Keyword(s):

Skeletal Muscle ◽

Fatty Acid ◽

Exercise Training ◽

Protein Expression ◽

Fatty Acid Oxidation ◽

Endurance Exercise ◽

Human Skeletal Muscle ◽

Acid Oxidation ◽

Endurance Exercise Training

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Peroxisomal Fatty Acid Oxidation Is a Substantial Source of the Acetyl Moiety of Malonyl-CoA in Rat Heart

Journal of Biological Chemistry ◽

10.1074/jbc.m400162200 ◽

2004 ◽

Vol 279 (19) ◽

pp. 19574-19579 ◽

Cited By ~ 52

Author(s):

Aneta E. Reszko ◽

Takhar Kasumov ◽

France David ◽

Kathryn A. Jobbins ◽

Katherine R. Thomas ◽

...

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

Acid Oxidation ◽

Acetyl Coa ◽

Mitochondrial Fatty Acid Oxidation ◽

Fatty Acid Chain ◽

Rat Hearts ◽

Malonyl Coa ◽

Mitochondrial Fatty Acid ◽

Perfused Rat Hearts

Little is known about the sources of acetyl-CoA used for the synthesis of malonyl-CoA, a key regulator of mitochondrial fatty acid oxidation in the heart. In perfused rat hearts, we previously showed that malonyl-CoA is labeled from both carbohydrates and fatty acids. This study was aimed at assessing the mechanisms of incorporation of fatty acid carbons into malonyl-CoA. Rat hearts were perfused with glucose, lactate, pyruvate, and a fatty acid (palmitate, oleate or docosanoate). In each experiment, substrates were13C-labeled to yield singly or/and doubly labeled acetyl-CoA. The mass isotopomer distribution of malonyl-CoA was compared with that of the acetyl moiety of citrate, which reflects mitochondrial acetyl-CoA. In the presence of labeled glucose or lactate/pyruvate, the13C labeling of malonyl-CoA was up to 2-fold lower than that of mitochondrial acetyl-CoA. However, in the presence of a fatty acid labeled in its first acetyl moiety, the13C labeling of malonyl-CoA was up to 10-fold higher than that of mitochondrial acetyl-CoA. The labeling of malonyl-CoA and of the acetyl moiety of citrate is compatible with peroxisomal β-oxidation forming C12and C14acyl-CoAs and contributing >50% of the fatty acid-derived acetyl groups that end up in malonyl-CoA. This fraction increases with the fatty acid chain length. By supplying acetyl-CoA for malonyl-CoA synthesis, peroxisomal β-oxidation may participate in the control of mitochondrial fatty acid oxidation in the heart. In addition, this pathway may supply some acyl groups used in protein acylation, which is increasingly recognized as an important regulatory mechanism for many biochemical processes.

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