Betaine supplementation causes increase in carnitine metabolites in the muscle and liver of mice fed a high-fat diet as studied by nontargeted LC-MS metabolomics approach

Pekkinen, Jenna; Olli, Kaisa; Huotari, Anne; Tiihonen, Kirsti; Keski‐Rahkonen, Pekka; Lehtonen, Marko; Auriola, Seppo; Kolehmainen, Marjukka; Mykkänen, Hannu; Poutanen, Kaisa; Hanhineva, Kati

doi:10.1002/mnfr.201300142

Cited by 65 publications

(57 citation statements)

References 55 publications

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“…These results are in line with previous studies which showed decreased TG content in the liver upon increasing betaine availability on adult mice [9,11]. In addition, studies also suggested that the effects of betaine on hepatic lipid deposition might also be through its ability to increase endogenous carnitine, as carnitine might increase carnitine palmitoyltransferase I-mediated fatty acid translocation into the mitochondria and β-oxidation [6,22]. Recently, the effects of betaine on the rectification of DNA methylation have also been declared to be a major mechanism accounting for the hepatoprotective effects of betaine [9,30].…”

Section: Discussionsupporting

confidence: 89%

FTO-dependent function of N6-methyladenosine is involved in the hepatoprotective effects of betaine on adolescent mice

Chen

Zhou

et al. 2015

J Physiol Biochem

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Nonalcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease among children and adolescents in the developed world. Betaine, as a methyl donor, recently has been demonstrated to exert its hepatoprotective effects through rectifying the genomic DNA hypomethylation state. However, whether betaine supplementation affects N6-methyladenosine (m(6)A) mRNA methylation in NAFLD is still unknown. We conducted the current study to investigate the effects of betaine supplementation during adolescence on high-fat diet-induced pathological changes in liver of mice, and we further identified the effects of betaine supplementation on expression of the fat mass and obesity-associated gene (FTO) and hepatic m(6)A mRNA methylation. Our results showed that betaine supplementation across adolescence significantly alleviated high-fat-induced impairment of liver function and morphology as well as ectopic fat accumulation. Surprisingly, no significant effects on serum TG and NEFA level, as well as fat mass, were observed in mice supplemented with betaine. We also found that high-fat diet upregulated ACC1 and FAS gene expression and downregulated HSL and ATGL gene expression. However, these alterations were rectified by betaine supplementation. Moreover, an m(6)A hypomethylation state and increased FTO expression were detected in mice fed with high-fat diet, while betaine supplementation prevented these changes. Our results suggested that betaine supplementation during adolescence could protect mice from high-fat-induced NAFLD by decreasing de novo lipogenesis and increasing lipolysis. Furthermore, a novel FTO-dependent function of m(6)A may involve in the hepatoprotective effects of betaine.

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Section: Discussionsupporting

confidence: 89%

FTO-dependent function of N6-methyladenosine is involved in the hepatoprotective effects of betaine on adolescent mice

Chen

Zhou

et al. 2015

J Physiol Biochem

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“…Hence, AMPK-ACC-CPT1 is an important signaling pathway to regulate fatty acid β-oxidation in mitochondria. Cai et al [44] found that gestational dietary betaine supplementation downregulated expression of ACC in neonatal piglets and Pekkinen et al [11] found betaine supplementation had an impact on carnitine metabolism in high-fat-fed mice. Our experiment didn't find significant changes in muscle concentrations of malonyl-CoA or carnitine.…”

Section: Discussionmentioning

confidence: 99%

“…Studies showed that dietary betaine supplementation affected energy partitioning in pigs [4,5] and it's also widely reported that betaine promotes animal growth and decreases carcass fat percentage in finishing pigs [6][7][8][9][10]. Further investigations found that betaine supplementation could decrease hepatic triglyceride accumulation [11,12] and prevent fatty liver in rats fed high-fat-diets [13,14]. The intramuscular fat content in the longissimus muscle was increased when pigs were fed betaine [15,16].…”

Section: Introductionmentioning

confidence: 99%

Betaine affects muscle lipid metabolism via regulating the fatty acid uptake and oxidation in finishing pig

Wang

et al. 2017

J Animal Sci Biotechnol

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Background: Betaine affects fat metabolism in animals, but the specific mechanism is still not clear. The purpose of this study was to investigate possible mechanisms of betaine in altering lipid metabolism in muscle tissue in finishing pigs. Methods: A total of 120 crossbred gilts (Landrace × Yorkshire × Duroc) with an average initial body weight of 70. 1 kg were randomly allotted to three dietary treatments. The treatments included a corn-soybean meal basal diet supplemented with 0, 1250 or 2500 mg/kg betaine. The feeding experiment lasted 42 d.

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“…7 The cardioprotective effect of long-term administration of mildronate, an inhibitor of carnitine biosynthesis, is associated with a decreased free carnitine concentration and increased GabaBet concentration, which correlates with the cardioprotection of mildronate. 25,26 Administration of betaine has an impact on carnitine metabolism, and this could further explain the link between betaine and lipid metabolism, 27 as evidenced by its ability to attenuate hepatic triglyceride accumulation. 28 Betaine may be particularly important for hepatic lipid metabolism, as betaine supplementation of mice with dietinduced obesity reduces hepatic lipids and improves whole body metabolism.…”

Section: Discussionmentioning

confidence: 99%

Gaba-betaine modulates SIRT1 and p16INK4A expression during high-glucose induced endothelial cell senescence

et al. 2017

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Gaba-betaine (γ-aminobutyric acid betaine, GabaBet), a betaine formed by trimethyllysine (TML), is a precursor of the L-carnitine biosynthesis. Betaine, quaternary ammonium compounds, are naturally occurring osmoprotectants or compatible solutes with a widespread distribution in plant and animal kingdoms. Among betaines, stachydrine (N,N-dimethyl-L-proline) (ProBet), abundant in citrus fruit juices, inhibits the deleterious effect of high-glucose (hGluc) on endothelial cells (EC). Hyperglycaemia induces endothelial dysfunction and vascular complications by promoting EC senescence, altering antioxidant enzyme involved in the system defence against reactive oxygen species (ROS), and limiting the cell proliferative potential. This study was designed to determine the possible effect of GabaBet against the hGluc-induced oxidative injury. Evaluation of cell viability revealed that GabaBet does not affect cell proliferation from 0.001 to 1mM up to 72 h. Of interest, co-treatment for 48 h with GabaBet (0.1 mM) and hGluc (30 mM) (GabaBet+hGluc) attenuated the EC growth arrest in the G0/G1 cell cycle phase. GabaBet counteracted the hGluc induced upregulation of p16 INK4A and the increased superoxide dismutase activity. Moreover, the downregulation of sirtuin 1 (SIRT1) expression, occurring under hGluc conditions, is significantly blocked by GabaBet. On the whole, results show that beneficial effects of GabaBet in the prevention of hGluc-induced endothelial senescence is paralleled by the modulation of SIRT1 and p16 INK4A expression levels.

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Betaine supplementation causes increase in carnitine metabolites in the muscle and liver of mice fed a high-fat diet as studied by nontargeted LC-MS metabolomics approach

Abstract: Our results suggest that increased availability of BET in different tissues, especially in muscle, after BET supplementation has an impact on carnitine metabolism, and this could further explain the link between BET and lipid metabolism.

Cited by 65 publications

References 55 publications

FTO-dependent function of N6-methyladenosine is involved in the hepatoprotective effects of betaine on adolescent mice

FTO-dependent function of N6-methyladenosine is involved in the hepatoprotective effects of betaine on adolescent mice

Betaine affects muscle lipid metabolism via regulating the fatty acid uptake and oxidation in finishing pig

Gaba-betaine modulates SIRT1 and p16INK4A expression during high-glucose induced endothelial cell senescence

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