The beneficial effects of betaine on dysfunctional adipose tissue and N6-methyladenosine mRNA methylation requires the AMP-activated protein kinase α1 subunit

Zhou, Xin; Chen, Jingqing; Chen, Jin; Wu, Wen‐Jer; Wang, Xinxia; Wang, Yizhen

doi:10.1016/j.jnutbio.2015.08.014

Cited by 54 publications

(44 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More recently, we found that inhibition of mRNA m 6 A methylation enhanced adipogenesis, while increasing the mRNA m 6 A methylation level suppressed adipogenesis in porcine adipocytes 22 . Furthermore, we also observed that m 6 A is involved in the metabolic effects of betaine on adipose tissue and liver 32 33 . However, the effects of mRNA m 6 A methylation on lipid metabolism in skeletal muscle remain unclear.…”

mentioning

confidence: 51%

AMPK regulates lipid accumulation in skeletal muscle cells through FTO-dependent demethylation of N6-methyladenosine

Feng

Jiang

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

Skeletal muscle plays important roles in whole-body energy homeostasis. Excessive skeletal muscle lipid accumulation is associated with some metabolic diseases such as obesity and Type 2 Diabetes. The energy sensor AMPK (AMP-activated protein kinase) is a key regulator of skeletal muscle lipid metabolism, but the precise regulatory mechanism remains to be elucidated. Here, we provide a novel mechanism by which AMPK regulates skeletal muscle lipid accumulation through fat mass and obesity-associated protein (FTO)-dependent demethylation of N6-methyladenosine (m6A). We confirmed an inverse correlation between AMPK and skeletal muscle lipid content. Moreover, inhibition of AMPK enhanced lipid accumulation, while activation of AMPK reduced lipid accumulation in skeletal muscle cells. Notably, we found that mRNA m6A methylation levels were inversely correlated with lipid content in skeletal muscle. Furthermore, AMPK positively regulated the m6A methylation levels of mRNA, which could negatively regulate lipid accumulation in C2C12. At the molecular level, we demonstrated that AMPK regulated lipid accumulation in skeletal muscle cells by regulating FTO expression and FTO-dependent demethylation of m6A. Together, these results provide a novel regulatory mechanism of AMPK on lipid metabolism in skeletal muscle cells and suggest the possibility of controlling skeletal muscle lipid deposition by targeting AMPK or using m6A related drugs.

show abstract

mentioning

confidence: 51%

AMPK regulates lipid accumulation in skeletal muscle cells through FTO-dependent demethylation of N6-methyladenosine

Feng

Jiang

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…As expected, serine supplementation significantly decreased oxidative stress in diquat-induced mice according to our results. Firstly, serine supplementation decreased plasma ALT and AST levels, which are indicators of liver injury [31], and also decreased LDH levels, which is a marker of cytoplasmic leakage caused by lipid peroxidation [33]. Secondary, serine prevented the increase of hepatic superoxide radical, hydrogen peroxide and TBARS contents, and rectified the decrease of GSH content, GSH/GSSG ratio and GSH-Px activity induced by diquat.…”

Section: Discussionmentioning

confidence: 97%

“…Samples were centrifuged at 13 000 rpm for 15 min after frequent vortexing for 20 min on ice. The supernatant was used for western blotting analysis as previous study did . In brief, 20 μg protein per lane were separated by SDS‐PAGE and blotted onto nitrocellulose membranes.…”

Section: Methodsmentioning

confidence: 99%

Serine alleviates oxidative stress via supporting glutathione synthesis and methionine cycle in mice

Zhou

et al. 2017

Molecular Nutrition Food Res

Self Cite

126

View full text Add to dashboard Cite

show abstract

“…Betaine (trimethylglycine) is a methyl donor that is possibly involved in the regulation of m 6 A. 19 Cells treated with different doses of betaine (0, 2, 4, and 8 mM) all showed increased m 6 A levels ( Figure 6A). To assess if betaine is toxic to cells, the MTT assay was performed.…”

Section: Betaine Up-regulated M 6 Levels and Inhibited Lipid Deposimentioning

confidence: 99%

FTO reduces mitochondria and promotes hepatic fat accumulation through RNA demethylation

Kang

Zhang

Lin

et al. 2018

J of Cellular Biochemistry

110

109

View full text Add to dashboard Cite

Fat mass and obesity-associated protein (FTO) is a RNA demethylase, whether FTO regulates fat metabolism through its demethylation is unclear. The results of this study confirmed that N6-methyladenosine (m A) is associated with fat accumulation both in vivo and in vitro. The data showed that FTO down-regulated m A levels, decreased mitochondrial content, and increased triglyceride (TG) deposition. However, an FTO (R316A) mutant lacking demethylation activity could not regulate mitochondria and TG content, indicating that FTO affects mitochondrial content and fat metabolism by modulating m A levels in hepatocytes. In addition, the regulatory roles of cycloleucine (methylation inhibitor) and betaine (methyl donor) could regulate m A levels and fat deposition. This work clarified that the demethylation function of FTO plays an essential role in the fat metabolism of hepatocytes and links the epigenetic modification of RNA with fat deposition, thereby providing a new target (m A) for regulation of hepatic fat metabolism.

show abstract

The beneficial effects of betaine on dysfunctional adipose tissue and N6-methyladenosine mRNA methylation requires the AMP-activated protein kinase α1 subunit

Cited by 54 publications

References 36 publications

AMPK regulates lipid accumulation in skeletal muscle cells through FTO-dependent demethylation of N6-methyladenosine

AMPK regulates lipid accumulation in skeletal muscle cells through FTO-dependent demethylation of N6-methyladenosine

Serine alleviates oxidative stress via supporting glutathione synthesis and methionine cycle in mice

FTO reduces mitochondria and promotes hepatic fat accumulation through RNA demethylation

Contact Info

Product

Resources

About