Methyl donor deficiency impairs fatty acid oxidation through PGC-1α hypomethylation and decreased ER-α, ERR-α, and HNF-4α in the rat liver

Pooya, Shabnam; Blaise, Sébastien; Garcia, Maira Moreno; Giudicelli, J.; Alberto, Jean-Marc; Guéant-Rodríguez, Rosa-María; Jeannesson, Élise; Guéguen, Naïg; Bressenot, Aude; Nicolas, Bénédicte; Malthièry, Yves; Daval, Jean‐Luc; Peyrin–Biroulet, Laurent; Bronowicki, Jean–Pierre; Guéant, Jean‐Louis

doi:10.1016/j.jhep.2012.03.028

Cited by 105 publications

(93 citation statements)

References 43 publications

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“…In groups fed with a MDD diet, folate and vitamin B12 concentrations were significantly decreased and HCY and SAH concentrations were significantly increased, as previously reported19 20 (see online supplementary figure S1).…”

Section: Resultssupporting

confidence: 85%

Methyl-deficient diet promotes colitis and SIRT1-mediated endoplasmic reticulum stress

Melhem

Hansmannel

Bressenot

et al. 2015

Gut

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Section: Resultssupporting

confidence: 85%

Methyl-deficient diet promotes colitis and SIRT1-mediated endoplasmic reticulum stress

Melhem

Hansmannel

Bressenot

et al. 2015

Gut

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“…In agreement with these mechanisms, we observed a reduced expression of PRMT-1 and a decreased SAM/SAH ratio, which led to a decreased methylation of ER-a, a decreased interaction between ER-a and PGC-1a, and an imbalanced detection of ER-a and PGC-1a in the cytoplasm and the nucleus of the deficient cells (30)(31)(32)(33). We have previously observed such a decreased interaction between PGC-1a and nuclear receptors through impaired methylation in the liver and the heart of MDD animals (1,(34)(35)(36). The impaired ER-a pathway led to decreased synapsins through decreased expression of the zinc finger transcriptional factor EGR-1/Zif-268.…”

Section: Discussionmentioning

confidence: 98%

Folate- and vitamin B₁₂–deficient diet during gestation and lactation alters cerebellar synapsin expressionviaimpaired influence of estrogen nuclear receptor α

Pourié¹,

Martin²,

Bossenmeyer‐Pourié³

et al. 2015

The FASEB Journal

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Deficiency in the methyl donors vitamin B 12 and folate during pregnancy and postnatal life impairs proper brain development. We studied the consequences of this combined deficiency on cerebellum plasticity in offspring from rat mothers subjected to deficient diet during gestation and lactation and in rat neuroprogenitor cells expressing cerebellum markers. The major proteomic change in cerebellum of 21-d-old deprived females was a 2.2-fold lower expression of synapsins, which was confirmed in neuroprogenitors cultivated in the deficient condition. A pathway analysis suggested that these proteomic changes were related to estrogen receptor a (ER-a)/Src tyrosine kinase. The influence of impaired ER-a pathway was confirmed by abnormal negative geotaxis test at d 19-20 and decreased phsophorylation of synapsins in deprived females treated by ER-a antagonist 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride (MPP). This effect was consistent with 2-fold decreased expression and methylation of ER-a and subsequent decreased ER-a/PPAR-g coactivator 1 a (PGC-1a) interaction in deficiency condition. The impaired ER-a pathway led to decreased expression of synapsins through 2-fold decreased EGR-1/Zif-268 transcription factor and to 1.7-fold reduced Src-dependent phosphorylation of synapsins. The treatment of neuroprogenitors with either MPP or PP1 (4-(49-phenoxyanilino)-6,7-dimethoxyquinazoline, 6,7-dimethoxy-N-(4-phenoxyphenyl)-4-quinazolinamine, SKI-1, Src-l1) Src inhibitor produced similar effects. In conclusion, the deficiency during pregnancy and lactation impairs the expression of synapsins through a deregulation of ER-a pathway.-Pourié, G., Martin, N., Bossenmeyer-Pourié, C., Akchiche, N., Guéant-Rodriguez, R. M., Geoffroy, A., Jeannesson, E., El Hajj Chehadeh, S., Mimoun, K., Brachet, P., Koziel, V., Alberto, J.-M., Helle, D., Debard, R., Leininger, B., Daval, J.-L., Guéant, J.-L. Folate-and vitamin B 12 -deficient diet during gestation and lactation alters cerebellar synapsin expression via impaired influence of estrogen nuclear receptor a. FASEB J. 29, 3713-3725 (2015). www.fasebj.org

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“…With regard to dietary changes in methyl-donors, it is of particular interest that PGC1α activity can be enhanced additionally by its methylation dependent on protein arginine methyltransferase 1 [52]. In this context, dietary methyl-donor deficiency was recently described to impair fatty acid oxidation through PGC1α hypomethylation in rat liver [39] and myocardium [53]. Interestingly, PGC1α is also known to influence homocysteine homeostasis, likely via hepatic nuclear factor 4α mediated expression control of BHMT [54].…”

Section: Discussionmentioning

confidence: 99%

Methyl-donor supplementation in obese mice prevents the progression of NAFLD, activates AMPK and decreases acyl-carnitine levels

Dahlhoff

Worsch

Sailer

et al. 2014

Molecular Metabolism

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Non-alcoholic fatty liver disease (NAFLD) results from increased hepatic lipid accumulation and steatosis, and is closely linked to liver one-carbon (C1) metabolism. We assessed in C57BL6/N mice whether NAFLD induced by a high-fat (HF) diet over 8 weeks can be reversed by additional 4 weeks of a dietary methyl-donor supplementation (MDS). MDS in the obese mice failed to reverse NAFLD, but prevented the progression of hepatic steatosis associated with major changes in key hepatic C1-metabolites, e.g. S-adenosyl-methionine and S-adenosyl-homocysteine. Increased phosphorylation of AMPK-α together with enhanced β-HAD activity suggested an increased flux through fatty acid oxidation pathways. This was supported by concomitantly decreased hepatic free fatty acid and acyl-carnitines levels. Although HF diet changed the hepatic phospholipid pattern, MDS did not. Our findings suggest that dietary methyl-donors activate AMPK, a key enzyme in fatty acid β-oxidation control, that mediates increased fatty acid utilization and thereby prevents further hepatic lipid accumulation.

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Methyl donor deficiency impairs fatty acid oxidation through PGC-1α hypomethylation and decreased ER-α, ERR-α, and HNF-4α in the rat liver

Cited by 105 publications

References 43 publications

Methyl-deficient diet promotes colitis and SIRT1-mediated endoplasmic reticulum stress

Methyl-deficient diet promotes colitis and SIRT1-mediated endoplasmic reticulum stress

Folate- and vitamin B₁₂–deficient diet during gestation and lactation alters cerebellar synapsin expressionviaimpaired influence of estrogen nuclear receptor α

Methyl-donor supplementation in obese mice prevents the progression of NAFLD, activates AMPK and decreases acyl-carnitine levels

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Methyl donor deficiency impairs fatty acid oxidation through PGC-1α hypomethylation and decreased ER-α, ERR-α, and HNF-4α in the rat liver

Cited by 105 publications

References 43 publications

Methyl-deficient diet promotes colitis and SIRT1-mediated endoplasmic reticulum stress

Methyl-deficient diet promotes colitis and SIRT1-mediated endoplasmic reticulum stress

Folate- and vitamin B12–deficient diet during gestation and lactation alters cerebellar synapsin expressionviaimpaired influence of estrogen nuclear receptor α

Methyl-donor supplementation in obese mice prevents the progression of NAFLD, activates AMPK and decreases acyl-carnitine levels

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Folate- and vitamin B₁₂–deficient diet during gestation and lactation alters cerebellar synapsin expressionviaimpaired influence of estrogen nuclear receptor α