TY  - JOUR
AU  - Vesković, Milena
AU  - Mladenović, Dušan
AU  - Milenković, Marina
AU  - Tosić, Jelena
AU  - Borozan, Sunčica
AU  - Gopcević, Kristina
AU  - Labudović-Borović, Milica
AU  - Dragutinović, Vesna
AU  - Vučević, Dragana
AU  - Jorgacević, Bojan
AU  - Isaković, Aleksandra
AU  - Trajković, Vladimir
AU  - Radosavljević, Tatjana
PY  - 2019
UR  - https://vet-erinar.vet.bg.ac.rs/handle/123456789/1727
AB  - We examined the effects of betaine, an endogenous and dietary methyl donor essential for the methionine-homocysteine cycle, on oxidative stress, inflammation, apoptosis, and autophagy in methionine-choline deficient diet (MCD)-induced non-alcoholic fatty liver disease (NAFLD). Male C57BL/6 mice received standard chow (control), standard chow and betaine (1.5% w/v in drinking water), MCD, or MCD and betaine. After six weeks, serum and liver samples were collected for analysis. Betaine reduced MCD-induced increase in liver transaminases and inflammatory infiltration, as well as hepatosteatosis and serum levels of low-density lipoprotein, while it increased that of high-density lipoprotein. MCD-induced hepatic production of reactive oxygen and nitrogen species was significantly reduced by betaine, which also improved liver antioxidative defense by increasing glutathione content and superoxide-dismutase, catalase, glutathione peroxidase, and paraoxonase activity. Betaine reduced the liver expression of proinflammatory cytokines tumor necrosis factor and interleukin-6, as well as that of proapoptotic mediator Box, while increasing the levels of anti-inflammatory cytokine interleukin-10 and antiapoptotic Bcl-2 in MCD-fed mice. In addition, betaine increased the expression of autophagy activators beclin 1, autophagy-related (Atg)4 and Atg5, as well as the presence of autophagic vesicles and degradation of autophagic target sequestosome 1/p62 in the liver of NAFLD mice. The observed effects of betaine coincided with the increase in the hepatic phosphorylation of mammalian target of rapamycin (mTOR) and its activator Akt. In conclusion, the beneficial effect of betaine in MCD-induced NAFLD is associated with the reduction of liver oxidative stress, inflammation, and apoptosis, and the increase in cytoprotective Akt/mTOR signaling and autophagy.
PB  - Elsevier Science Bv, Amsterdam
T2  - European Journal of Pharmacology
T1  - Betaine modulates oxidative stress, inflammation, apoptosis, autophagy, and Akt/mTOR signaling in methionine-choline deficiency-induced fatty liver disease
VL  - 848
SP  - 39
EP  - 48
DO  - 10.1016/j.ejphar.2019.01.043
ER  - 

@article{
author = "Vesković, Milena and Mladenović, Dušan and Milenković, Marina and Tosić, Jelena and Borozan, Sunčica and Gopcević, Kristina and Labudović-Borović, Milica and Dragutinović, Vesna and Vučević, Dragana and Jorgacević, Bojan and Isaković, Aleksandra and Trajković, Vladimir and Radosavljević, Tatjana",
year = "2019",
abstract = "We examined the effects of betaine, an endogenous and dietary methyl donor essential for the methionine-homocysteine cycle, on oxidative stress, inflammation, apoptosis, and autophagy in methionine-choline deficient diet (MCD)-induced non-alcoholic fatty liver disease (NAFLD). Male C57BL/6 mice received standard chow (control), standard chow and betaine (1.5% w/v in drinking water), MCD, or MCD and betaine. After six weeks, serum and liver samples were collected for analysis. Betaine reduced MCD-induced increase in liver transaminases and inflammatory infiltration, as well as hepatosteatosis and serum levels of low-density lipoprotein, while it increased that of high-density lipoprotein. MCD-induced hepatic production of reactive oxygen and nitrogen species was significantly reduced by betaine, which also improved liver antioxidative defense by increasing glutathione content and superoxide-dismutase, catalase, glutathione peroxidase, and paraoxonase activity. Betaine reduced the liver expression of proinflammatory cytokines tumor necrosis factor and interleukin-6, as well as that of proapoptotic mediator Box, while increasing the levels of anti-inflammatory cytokine interleukin-10 and antiapoptotic Bcl-2 in MCD-fed mice. In addition, betaine increased the expression of autophagy activators beclin 1, autophagy-related (Atg)4 and Atg5, as well as the presence of autophagic vesicles and degradation of autophagic target sequestosome 1/p62 in the liver of NAFLD mice. The observed effects of betaine coincided with the increase in the hepatic phosphorylation of mammalian target of rapamycin (mTOR) and its activator Akt. In conclusion, the beneficial effect of betaine in MCD-induced NAFLD is associated with the reduction of liver oxidative stress, inflammation, and apoptosis, and the increase in cytoprotective Akt/mTOR signaling and autophagy.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "European Journal of Pharmacology",
title = "Betaine modulates oxidative stress, inflammation, apoptosis, autophagy, and Akt/mTOR signaling in methionine-choline deficiency-induced fatty liver disease",
volume = "848",
pages = "39-48",
doi = "10.1016/j.ejphar.2019.01.043"
}

Vesković, M., Mladenović, D., Milenković, M., Tosić, J., Borozan, S., Gopcević, K., Labudović-Borović, M., Dragutinović, V., Vučević, D., Jorgacević, B., Isaković, A., Trajković, V.,& Radosavljević, T.. (2019). Betaine modulates oxidative stress, inflammation, apoptosis, autophagy, and Akt/mTOR signaling in methionine-choline deficiency-induced fatty liver disease. in European Journal of Pharmacology
Elsevier Science Bv, Amsterdam., 848, 39-48.
https://doi.org/10.1016/j.ejphar.2019.01.043

Vesković M, Mladenović D, Milenković M, Tosić J, Borozan S, Gopcević K, Labudović-Borović M, Dragutinović V, Vučević D, Jorgacević B, Isaković A, Trajković V, Radosavljević T. Betaine modulates oxidative stress, inflammation, apoptosis, autophagy, and Akt/mTOR signaling in methionine-choline deficiency-induced fatty liver disease. in European Journal of Pharmacology. 2019;848:39-48.
doi:10.1016/j.ejphar.2019.01.043 .

Vesković, Milena, Mladenović, Dušan, Milenković, Marina, Tosić, Jelena, Borozan, Sunčica, Gopcević, Kristina, Labudović-Borović, Milica, Dragutinović, Vesna, Vučević, Dragana, Jorgacević, Bojan, Isaković, Aleksandra, Trajković, Vladimir, Radosavljević, Tatjana, "Betaine modulates oxidative stress, inflammation, apoptosis, autophagy, and Akt/mTOR signaling in methionine-choline deficiency-induced fatty liver disease" in European Journal of Pharmacology, 848 (2019):39-48,
https://doi.org/10.1016/j.ejphar.2019.01.043 . .