The effect of short-term methionine restriction on glutathione synthetic capacity and antioxidant responses at the whole tissue and mitochondrial level in the rat liver

Tamanna, Nahid; Kroeker, Kristine; Braun, Kristen; Banh, Sheena; Treberg, Jason R.

doi:10.1016/j.exger.2019.110712

Cited by 18 publications

(10 citation statements)

References 67 publications

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“…However, GSH concentrations were reduced in the liver [31,50]. Despite the MR-induced reduction in hepatic GSH, MR does not increase oxidative stress, in part because MR enhances antioxidant capacity and increases proton leak in the liver, likely decreasing ROS production [51]. The ability of MR to increase GSH levels in red blood cells is significant because of the role of GSH in the neutralization of ROS [52].…”

Section: Glutathione Formationmentioning

confidence: 99%

Methionine Restriction and Cancer Biology

2020

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The essential amino acid, methionine, is important for cancer cell growth and metabolism. A growing body of evidence indicates that methionine restriction inhibits cancer cell growth and may enhance the efficacy of chemotherapeutic agents. This review summarizes the efficacy and mechanism of action of methionine restriction on hallmarks of cancer in vitro and in vivo. The review highlights the role of glutathione formation, polyamine synthesis, and methyl group donation as mediators of the effects of methionine restriction on cancer biology. The translational potential of the use of methionine restriction as a personalized nutritional approach for the treatment of patients with cancer is also discussed.

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Section: Glutathione Formationmentioning

confidence: 99%

Methionine Restriction and Cancer Biology

2020

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“…Previous studies have shown MR to have a variety of impacts on mitochondrial function 8 , 13 – 18 , 41 , 42 . Here we expand on these findings and point to sex- and tissue-specific differences in mitochondrial response to MR as well as potential roles for methionine oxidation repair via MsrA in this process.…”

Section: Discussionmentioning

confidence: 99%

Sulfur Amino Acid Restriction alters mitochondrial function depending on tissue, sex, and Methionine sulfoxide reductase A (MsrA) status.

Thyne,

Camones,

Salmon

2023

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Methionine restriction (MR) has been shown to affect mitochondrial function including altering oxygen consumption, reactive oxygen species (ROS) generation, Complex expression, and oxidative damage. The sulfur-containing amino acid methionine can become oxidized forming methionine sulfoxide which can lead to changes in protein function and signaling. Methionine sulfoxide reductases are endogenous enzymes capable of reducing methionine sulfoxide, with Methionine sulfoxide reductase A (MsrA) being ubiquitously expressed in mammals. Here we investigated if the effects of MR on mitochondrial function required functional MsrA in the liver and kidney which are the major tissues involved in sulfur biochemistry and both highly express MsrA. Moreover, MsrA is endogenously found in the mitochondria thereby providing potential mechanisms linking diet to mitochondrial phenotype. We found sex-specific changes in oxygen consumption of isolated mitochondria and females showed changes with MR in a tissue-dependent manner – increased in liver and decreased in kidney. Loss of MsrA increased or decreased oxygen consumption depending on the tissue and which portion of the electron transport chain was being tested. In general, males had few changes in either tissue regardless of MR or MsrA status. Hydrogen peroxide production was increased in the kidney with MR regardless of sex or MsrA status. However, in the liver, production was increased by MR in females and only slightly higher with loss of MsrA in both sexes. Mitochondrial Complex expression was found to be largely unchanged in either tissue suggesting these effects are driven by regulatory mechanisms and not by changes in expression. Together these results suggest that sex and MsrA status do impact the mitochondrial effects of MR in a tissue-specific manner.

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“…Homocysteine generated via the methionine cycle is also a precursor for synthesis of the antioxidant glutathione. Therefore, decreased entry of methionine into the methionine cycle is expected to result not only in depletion of SAM but also decreased production of glutathione, as indeed seen in some cases with methionine restricted diets 27,28 and, more directly, with knockout or silencing of MAT1A 29 . An excess of SAM is as injurious as its depletion, and may lead to the development of hepatic steatosis 30,31 .…”

Section: Introductionmentioning

confidence: 96%

A multiomics comparison of weight loss interventions shows the distinct effects of bariatric surgery and intermittent fasting on hepatic metabolism

Haran

Bergel

Kleiman

et al. 2022

Preprint

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The prevalence of obesity and non-alcoholic fatty liver (NAFL) is steadily increasing. Weight loss can lead to improvement in NAFL in patients and in model organisms. Weight loss can be achieved through either dietary and lifestyle interventions, pharmacotherapy, and bariatric surgery. Some interventions, such as intermittent fasting, have been purported to have benefits beyond those conferred by weight loss alone. In this study, rats were provided a high-fat, high-sucrose diet for 7 weeks and then were assigned to strict caloric restriction with intermittent fasting (IF-CR) or to sleeve gastrectomy (SG) bariatric surgery, achieving equivalent weight loss. The two interventions were compared to ad-libitum fed controls. The metabolome of the blood entering the liver was analyzed in the three experimental groups, as well as the metabolome and transcriptome of the liver under fasting conditions, to test how different means of weight loss affect the input of the liver and hepatic metabolism. Surprisingly, the two interventions had different and often opposite effects on the composition of portal blood and liver metabolites. IF-CR resulted in sweeping changes across multiple central metabolic pathways, including an increase in de novo lipogenesis and triglyceride export, and upregulation of glycolysis, citric acid cycle, and the pentose phosphate pathway, as well as an increase in glycogen storage. Meanwhile, the effects of SG concentrated on one-carbon metabolic pathways, with changes in metabolite and transcript levels pointing to decreased transmethylation and methionine cycle activity, with downstream effects on levels of glutathione and the hepatic oxidative state. In conclusion, our study highlights how different means of weight loss affect distinct metabolic pathways and demonstrates a unique effect of bariatric surgery on hepatic one-carbon and redox pathways.

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The effect of short-term methionine restriction on glutathione synthetic capacity and antioxidant responses at the whole tissue and mitochondrial level in the rat liver

Cited by 18 publications

References 67 publications

Methionine Restriction and Cancer Biology

Methionine Restriction and Cancer Biology

Sulfur Amino Acid Restriction alters mitochondrial function depending on tissue, sex, and Methionine sulfoxide reductase A (MsrA) status.

A multiomics comparison of weight loss interventions shows the distinct effects of bariatric surgery and intermittent fasting on hepatic metabolism

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