Methionine restriction effects on mitochondrial biogenesis and aerobic capacity in white adipose tissue, liver, and skeletal muscle of F344 rats

Perrone, Carmen E.; Mattocks, Dwight A.L.; Jarvis-Morar, Maureen; Plummer, Jason D.; Orentreich, Norman

doi:10.1016/j.metabol.2009.10.023

Cited by 107 publications

(120 citation statements)

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“…TaqMan quantitative PCR (qPCR) was conducted as described previously [6]. Total RNA (n = 7–8 per tissue and treatment group) was used for cDNA preparation with the High-Capacity cDNA Reverse Transcription Kit (Life Technologies Corp., Carlsbad, Calif., USA) in a Perkin-Elmer GeneAmp PCR System 9600 and the cDNA was then used in multiplexed qPCR in a StepOnePlus Real-Time PCR System (Life Technologies Corp.) using commercially available primer-probe sets (online supp.…”

Section: Methodsmentioning

confidence: 99%

“…For Western blot analysis, tissue homogenates (n = 6–8 per tissue and treatment group) were prepared as described previously [4,6]. Fifty micrograms of protein were electrophoresed in 4–20% SDS-PAGE gradient gels, the proteins were transferred to PVDF membranes, and the membranes were incubated overnight at 4°C with primary antibodies (Abs).…”

Section: Methodsmentioning

confidence: 99%

“…Insulin sensitivity in MR rats is associated with reduced fat accretion, a response involving metabolic adaptations that alter lipid metabolism [4]. Decreased adiposity is also associated with increased energy expenditure [3,5] corresponding with the upregulation of peroxisome proliferator-activated receptor γ (PPARγ), PPARγ coactivator 1α (PGC1a) and their target genes, which leads to mitochondrial biogenesis in adipose tissues and increased mitochondrial aerobic capacity of liver and quadriceps muscle from MR rats [6]. …”

Section: Introductionmentioning

confidence: 99%

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Genomic and Metabolic Responses to Methionine-Restricted and Methionine-Restricted, Cysteine-Supplemented Diets in Fischer 344 Rat Inguinal Adipose Tissue, Liver and Quadriceps Muscle

et al. 2012

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Background/Aims: Methionine restriction (MR) is a dietary intervention that increases lifespan, reduces adiposity and improves insulin sensitivity. These effects are reversed by supplementation of the MR diet with cysteine (MRC). Genomic and metabolomic studies were conducted to identify potential mechanisms by which MR induces favorable metabolic effects, and that are reversed by cysteine supplementation. Methods: Gene expression was examined by microarray analysis and TaqMan quantitative PCR. Levels of selected proteins were measured by Western blot and metabolic intermediates were analyzed by mass spectrometry. Results: MR increased lipid metabolism in inguinal adipose tissue and quadriceps muscle while it decreased lipid synthesis in liver. In inguinal adipose tissue, MR not only caused the transcriptional upregulation of genes associated with fatty acid synthesis but also of Lpin1, Pc, Pck1 and Pdk1, genes that are associated with glyceroneogenesis. MR also upregulated lipolysis-associated genes in inguinal fat and led to increased oxidation in this tissue, as suggested by higher levels of methionine sulfoxide and 13-HODE + 9-HODE compared to control-fed (CF) rats. Moreover, MR caused a trend toward the downregulation of inflammation-associated genes in inguinal adipose tissue. MRC reversed most gene and metabolite changes induced by MR in inguinal adipose tissue, but drove the expression of Elovl6, Lpin1, Pc, and Pdk1 below CF levels. In liver, MR decreased levels of a number of long-chain fatty acids, glycerol and glycerol-3-phosphate corresponding with the gene expression data. Although MR increased the expression of genes associated with carbohydrate metabolism, levels of glycolytic intermediates were below CF levels. MR, however, stimulated gluconeogenesis and ketogenesis in liver tissue. As previously reported, sulfur amino acids derived from methionine were decreased in liver by MR, but homocysteine levels were elevated. Increased liver homocysteine levels by MR were associated with decreased cystathionine β-synthase (CBS) protein levels and lowered vitamin B6 and 5-methyltetrahydrofolate (5MeTHF) content. Finally, MR upregulated fibroblast growth factor 21 (FGF21) gene and protein levels in both liver and adipose tissues. MRC reversed some of MR’s effects in liver and upregulated the transcription of genes associated with inflammation and carcinogenesis such as Cxcl16, Cdh17, Mmp12, Mybl1, and Cav1 among others. In quadriceps muscle, MR upregulated lipid metabolism-associated genes and increased 3-hydroxybutyrate levels suggesting increased fatty acid oxidation as well as stimulation of gluconeogenesis and glycogenolysis in this tissue. Conclusion: Increased lipid metabolism in inguinal adipose tissue and quadriceps muscle, decreased triglyceride synthesis in liver and the downregulation of inflammation-associated genes are among the factors that could favor the lean phenotype and increased insulin sensitivity observed in MR rats.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genomic and Metabolic Responses to Methionine-Restricted and Methionine-Restricted, Cysteine-Supplemented Diets in Fischer 344 Rat Inguinal Adipose Tissue, Liver and Quadriceps Muscle

et al. 2012

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“…Studies examining the restriction of the essential amino acid and glutathione precursor methionine found it not only to be lifespan extending. Increasing mitochondrial biogenesis and function, energy expenditure, stress resistance, aerobic capacity, insulin sensitivity, glutathione (GSH) and expression of glutathione-S-transferase (GST) as well as a decrease of oxidative stress and cell damage due to adaptive changes in methionine and GSH metabolism were also observed (Zimmerman et al 2003, Miller et al 2005, Perrone et al 2010, Richie et al 1994, Malloy et al 2006, Sanz et al 2006, Perrone et al 2012, Tsai et al 2010, Caro et al 2008. Interestingly, co-treatment with an antioxidant, N-acetylcysteine, blocks some of the health-promoting effects of methionine restriction, accentuating a critical role for ROS with mitohormetic adaption processes in this regard (Elshorbagy et al 2012, Sanchez-Roman et al 2012).…”

Section: Mitochondrial Hormesis and Lifespanmentioning

confidence: 99%

Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS)

2014

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ᮀ Increasing evidence indicates that reactive oxygen species (ROS), consisting of superoxide, hydrogen peroxide, and multiple others, do not only cause oxidative stress, but rather may function as signaling molecules that promote health by preventing or delaying a number of chronic diseases, and ultimately extend lifespan. While high levels of ROS are generally accepted to cause cellular damage and to promote aging, low levels of these may rather improve systemic defense mechanisms by inducing an adaptive response. This concept has been named mitochondrial hormesis or mitohormesis. We here evaluate and summarize more than 500 publications from current literature regarding such ROS-mediated low-dose signaling events, including calorie restriction, hypoxia, temperature stress, and physical activity, as well as signaling events downstream of insulin/IGF-1 receptors, AMP-dependent kinase (AMPK), target-of-rapamycin (TOR), and lastly sirtuins to culminate in control of proteostasis, unfolded protein response (UPR), stem cell maintenance and stress resistance. Additionally, consequences of interfering with such ROS signals by pharmacological or natural compounds are being discussed, concluding that particularly antioxidants are useless or even harmful.

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“…Additionally, CS has been used as an index of mitochondrial respiratory activity and mitochondrial biogenesis in WAT (9,24). Loss of ␣ 1 -AMPK had no effect on CS activity in BAT or other tissues (Table 2).…”

Section: R477 Responses To Cold and Thermogenesis Of Ampk ϫ/ϫ Micementioning

confidence: 99%

Cold tolerance, cold-induced hyperphagia, and nonshivering thermogenesis are normal in α₁-AMPK^−/−mice

Bauwens¹,

Schmuck

Lindholm³

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Methionine restriction effects on mitochondrial biogenesis and aerobic capacity in white adipose tissue, liver, and skeletal muscle of F344 rats

Cited by 107 publications

References 68 publications

Genomic and Metabolic Responses to Methionine-Restricted and Methionine-Restricted, Cysteine-Supplemented Diets in Fischer 344 Rat Inguinal Adipose Tissue, Liver and Quadriceps Muscle

Genomic and Metabolic Responses to Methionine-Restricted and Methionine-Restricted, Cysteine-Supplemented Diets in Fischer 344 Rat Inguinal Adipose Tissue, Liver and Quadriceps Muscle

Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS)

Cold tolerance, cold-induced hyperphagia, and nonshivering thermogenesis are normal in α₁-AMPK^−/−mice

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Methionine restriction effects on mitochondrial biogenesis and aerobic capacity in white adipose tissue, liver, and skeletal muscle of F344 rats

Cited by 107 publications

References 68 publications

Genomic and Metabolic Responses to Methionine-Restricted and Methionine-Restricted, Cysteine-Supplemented Diets in Fischer 344 Rat Inguinal Adipose Tissue, Liver and Quadriceps Muscle

Genomic and Metabolic Responses to Methionine-Restricted and Methionine-Restricted, Cysteine-Supplemented Diets in Fischer 344 Rat Inguinal Adipose Tissue, Liver and Quadriceps Muscle

Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS)

Cold tolerance, cold-induced hyperphagia, and nonshivering thermogenesis are normal in α1-AMPK−/−mice

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Cold tolerance, cold-induced hyperphagia, and nonshivering thermogenesis are normal in α₁-AMPK^−/−mice