Betaine modulates oxidative stress, inflammation, apoptosis, autophagy, and Akt/mTOR signaling in methionine-choline deficiency-induced fatty liver disease

Vesković, Milena; Mladenović, Dušan; Milenković, Marina; Tošić, Jelena; Borozan, Sunčica; Gopčević, Kristina; Labudović‐Borović, Milica; Dragutinović, Vesna; Vučević, Danijela; Jorgačević, Bojan; Isaković, Aleksandra; Trajkovič, Vladimir; Radosavljević, Tatjana

doi:10.1016/j.ejphar.2019.01.043

Cited by 119 publications

(94 citation statements)

References 68 publications

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“…Both choline and betaine, as the precursor substances of trimethylamine N‐oxide (TMAO), are two essential and nutritional biomolecules. Several reports demonstrated that the deficiency of choline and betaine could accelerate the production of reactive oxygen species (ROS) and are thus considered as a key factor in initiating and maintaining inflammatory diseases caused by oxidative damage [35,36]. Recent studies indicated that the absence of the essential amino acid L‐tryptophan could affect ROS scavenging and immune response control in vitiligo, which is generally regarded as an autoimmune disease and which is also a prominent feature in VKH disease [5,37].…”

Section: Discussionmentioning

confidence: 99%

Integrated omics analysis of sweat reveals an aberrant amino acid metabolism pathway in Vogt–Koyanagi–Harada disease

Cui

Zhang

et al. 2020

Clinical and Experimental Immunology

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Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disease leading to visual impairment. Its pathogenic mechanisms remain poorly understood. Our purpose was to investigate the distinctive protein and metabolic profiles of sweat in patients with VKH disease. In the present study, proteomics and metabolomics analysis was performed on 60 sweat samples (30 VKH patients and 30 normal controls) using liquid chromatography tandem mass spectrometry. Parallel reaction monitoring (PRM) analysis was used to validate the results of our omics analysis. In total, we were able to detect 716 proteins and 175 metabolites. Among them, 116 proteins (99 decreased and 17 increased) were observed to be significantly different in VKH patients when compared to controls. Twenty-one differentially expressed metabolites were identified in VKH patients, of which 18 included choline, L-tryptophan, betaine and L-serine were reduced, while the rest were increased. Our multi-omics strategy reveals an important role for the amino acid metabolic pathway in the pathogenesis of VKH disease. Significant differences in proteins and metabolites were identified in the sweat of VKH patients and, to some extent, an aberrant amino acid metabolism pathway may be a pathogenic factor in the pathogenesis of VKH disease.

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Section: Discussionmentioning

confidence: 99%

Integrated omics analysis of sweat reveals an aberrant amino acid metabolism pathway in Vogt–Koyanagi–Harada disease

Cui

Zhang

et al. 2020

Clinical and Experimental Immunology

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“…The study of FLS is difficult because of its obscure features and irregular occurrence. Usually, nutrients supplement is widely applied for the prevention of FLS, such as choline [11], betaine [12], polyunsaturated fatty acid [13], and conjugated linoleic acid [14]. However, this approach is costly and not precise enough.…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Detection of Key Genes and Epigenetic Markers for Chicken Fatty Liver

Tan

Liu

Xing

et al. 2020

IJMS

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Chickens are one of the most important sources of meat worldwide, and the occurrence of fatty liver syndrome (FLS) is closely related to production efficiency. However, the potential mechanism of FLS remains poorly understood. An integrated analysis of data from whole-genome bisulfite sequencing and long noncoding RNA (lncRNA) sequencing was conducted. A total of 1177 differentially expressed genes (DEGs) and 1442 differentially methylated genes (DMGs) were found. There were 72% of 83 lipid- and glucose-related genes upregulated; 81% of 150 immune-related genes were downregulated in fatty livers. Part of those genes was within differentially methylated regions (DMRs). Besides, sixty-seven lncRNAs were identified differentially expressed and divided into 13 clusters based on their expression pattern. Some lipid- and glucose-related lncRNAs (e.g., LNC_006756, LNC_012355, and LNC_005024) and immune-related lncRNAs (e.g., LNC_010111, LNC_010862, and LNC_001272) were found through a co-expression network and functional annotation. From the expression and epigenetic profiles, 23 target genes (e.g., HAO1, ABCD3, and BLMH) were found to be hub genes that were regulated by both methylation and lncRNAs. We have provided comprehensive epigenetic and transcriptomic profiles on FLS in chicken, and the identification of key genes and epigenetic markers will expand our understanding of the molecular mechanism of chicken FLS.

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“…acid, triglycerides, and VLDL efflux from the liver as well as by increasing sensitivity of hormone-dependent lipase in the adipose tissue (Yang et al, 2016;Veskovic et al, 2019). After 6 weeks with the MCD diet, micro-and macrovesicular steatosis were detected in electron microphotographs as well (Fig.…”

Section: Discussionmentioning

confidence: 91%

“…In animals fed with the MCD diet, betaine treatment significantly increased the autophagosome number in hepatocytes, compared to the MCD group. On the same animal model, our recent study showed that betaine stimulated autophagy by the activation of Akt/mTOR signaling pathway (Veskovic et al, 2019). Induction of lipophagy in NAFLD may lead to the removal of accumulated lipids from hepatocytes (Schulze et al, 2017) that may represent an additional hepatoprotective mechanism of betaine.…”

Section: Discussionmentioning

confidence: 94%

Effect of Betaine Supplementation on Liver Tissue and Ultrastructural Changes in Methionine–Choline-Deficient Diet-Induced NAFLD

et al. 2020

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Nonalcoholic fatty liver disease (NAFLD) represents a hepatic manifestation of metabolic syndrome. The aim of this study was to examine the effect of betaine on ultrastructural changes in the mouse liver with methionine- and choline-deficient (MCD) diet-induced NAFLD. Male C57BL/6 mice were divided into groups: Control—fed with standard chow, BET—standard chow supplemented with betaine (1.5% w/v drinking water), MCD—fed with MCD diet, and MCD + BET—MCD diet with betaine supplementation for 6 weeks. Liver samples were taken for pathohistology and transmission electron microscopy. The MCD diet-induced steatosis, inflammation, and balloon-altered hepatocytes were alleviated by betaine. MCD diet induced an increase in mitochondrial size versus the control group (p < 0.01), which was decreased in the betaine-treated group. In the MCD diet-fed group, the total mitochondrial count decreased versus the control group (p < 0.01), while it increased in the MCD + BET group versus MCD (p < 0.01). Electron microscopy showed an increase in the number of autophagosomes in the MCD and MCD + BET group versus control, and a significant difference in autophagosomes number was detected in the MCD + BET group by comparison with the MCD diet-treated group (p < 0.05). Betaine decreases the number of enlarged mitochondria, alleviates steatosis, and increases the number of autophagosomes in the liver of mice with NAFLD.

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Betaine modulates oxidative stress, inflammation, apoptosis, autophagy, and Akt/mTOR signaling in methionine-choline deficiency-induced fatty liver disease

Cited by 119 publications

References 68 publications

Integrated omics analysis of sweat reveals an aberrant amino acid metabolism pathway in Vogt–Koyanagi–Harada disease

Integrated omics analysis of sweat reveals an aberrant amino acid metabolism pathway in Vogt–Koyanagi–Harada disease

Genome-Wide Detection of Key Genes and Epigenetic Markers for Chicken Fatty Liver

Effect of Betaine Supplementation on Liver Tissue and Ultrastructural Changes in Methionine–Choline-Deficient Diet-Induced NAFLD

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