mRNA m6A methylation downregulates adipogenesis in porcine adipocytes

Wang, Xinxia; Zhu, Liangjun; Chen, Jingqing; Wang, Yizhen

doi:10.1016/j.bbrc.2015.02.048

Cited by 102 publications

(109 citation statements)

References 22 publications

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“…There was a similar result indicating that mRNA m 6 A levels downregulate adipogenesis in porcine adipocytes [20]. Other reports show that demethylation of mRNA m 6 A is required for the adipogenesis of the 3T3-L1 preadipocyte cell line [21,22].…”

Section: Discussionmentioning

confidence: 55%

“…That may be one of the reasons why FTO overexpression promotes obesity [23], and inactive FTO competes with and suppresses obesity [24]. In contrast to FTO, overexpression of METTL3, a critical component of the multiprotein methyltransferase complex for m 6 A methylation [4], could inhibit the expression of pro-adipogenic genes such as PPARγ, and thus suppress adipogenesis and reduce cellular triglyceride content [20]. Taken together, our data show that the m 6 A system may be involved in the adipose tissue development programmed by maternal nutrition.…”

Section: Discussionmentioning

confidence: 99%

“…As for m 6 A related genes, both FTO and METTL3 were simultaneously elevated in the HFD group at eight weeks of age (Figure 4), which was puzzling as their physiological functions are assumed to be contradictory [5,6]. We suppose that this may be due to a compensatory mechanism, for there are indeed several documents describing the mismatch of METTL3 [20] and FTO [25,26] expression with m 6 A levels, especially under physiological conditions where many complicated compensatory pathways exist, and small differences in conditions could affect m 6 A levels.…”

Section: Discussionmentioning

confidence: 99%

“…RNA dot-blot was conducted strictly as previously reported [20]. Firstly, an aliquot of 200 ng mRNA was denatured by heating at 95 °C for 3 min, and immediately cooled down on ice.…”

Section: Methodsmentioning

confidence: 99%

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Mouse Maternal High-Fat Intake Dynamically Programmed mRNA m6A Modifications in Adipose and Skeletal Muscle Tissues in Offspring

Yang

Zhu

et al. 2016

IJMS

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Epigenetic mechanisms have an important role in the pre- and peri-conceptional programming by maternal nutrition. Yet, whether or not RNA m6A methylation—an old epigenetic marker receiving increased attention recently—is involved remains an unknown question. In this study, mouse high-fat feeding prior to conception was shown to induce overweight and glucose intolerant dams, which then continued to be exposed to a high-fat diet during gestation and lactation. The dams on a standard diet throughout the whole experiment were used as a control. Results showed that maternal high-fat intake impaired postnatal growth in male offspring, indicated by decreased body weight and Lee’s index at 3, 8 and 15 weeks old, but the percentages of visceral fat and tibialis anterior relative to the whole body weights were significantly increased at eight weeks of age. The maternal high-fat exposure significantly increased mRNA N6-methyladenosine (m6A) levels in visceral fat at three weeks old, combined with downregulated Fat mass and obesity-associated gene (FTO) and upregulated Methyltransferase like 3 (METTL3) transcription, and these changes were reversed at eight weeks of age. In the tibialis anterior muscle, the maternal high-fat diet significantly enhanced m6A modifications at three weeks, and lowered m6A levels at 15 weeks of age. Accordingly, FTO transcription was significantly inhibited at three weeks and stimulated at 15 weeks of age, and METTL3 transcripts were significantly improved at three weeks. Interestingly, both FTO and METTL3 transcription was significantly elevated at eight weeks of age, and yet the m6A modifications remained unchanged. Our study showed that maternal high-fat intake could affect mRNA m6A modifications and its related genes in offspring in a tissue-specific and development-dependent way, and provided an interesting indication of the working of the m6A system during the transmission from maternal nutrition to subsequent generations.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…RNA dot-blot was conducted strictly as previously reported [20]. Firstly, an aliquot of 200 ng mRNA was denatured by heating at 95 °C for 3 min, and immediately cooled down on ice.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Mouse Maternal High-Fat Intake Dynamically Programmed mRNA m6A Modifications in Adipose and Skeletal Muscle Tissues in Offspring

Yang

Zhu

et al. 2016

IJMS

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“…In addition, our group found mRNA m 6 A methylation is negative related to adipogenesis in pig. Exogenous methylation inhibitor and methyl donors affect adipogenesis by regulating mRNA m 6 A level (Wang et al, ). We demonstrated that AMPK regulated lipid accumulation in skeletal muscle cells by regulating FTO expression and FTO‐dependent demethylation of m 6 A (Wu et al, ).…”

Section: The Biological Functions Of M6amentioning

confidence: 99%

A dynamic reversible RNA N⁶‐methyladenosine modification: current status and perspectives

Liu

Zhao

et al. 2019

Journal Cellular Physiology

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107

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N6‐methyladenosine (m6A), as the most abundant RNA epigenetic modifications, has been shown to play critical roles in various biological functions. Research about enzymes that can catalyze and remove m6A have revealed its comprehensive roles in messenger RNA (mRNA) metabolism and other physiological processes. The “readers” including YTH domain‐containing proteins, hnRNPC, hnRNPG, hnRNPA2B1, IGF2BP1, IGF2BP2, and IGF2BP3, which can affect the fates of mRNA in an m6A‐dependent manner. In this review, we focus on recent advances in the research of the m6A modifications, especially about the latest functions of its writers, erasers, readers in RNA metabolism, cancer, and lipid metabolism. In the end, we provide insights into the underlying molecular mechanisms of m6A modifications.

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Novel Insights into Adipogenesis from the Perspective of Transcriptional and RNA N6‐Methyladenosine‐Mediated Post‐Transcriptional Regulation

et al. 2020

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Obesity is a critical risk factor causing the development of metabolic diseases and cancers. Its increasing prevalence worldwide has aroused great concerns of the researchers on adipose development and metabolic function. During adipose expansion, adipogenesis is a way to store lipids as well as to avoid lipotoxicity in other tissues, and may be an approach to offset the negative metabolic effects of obesity. In this Review, the transcriptional regulation of adipogenesis is outlined to characterize numerous biological processes in research on the determination of adipocyte fate and regulation of adipogenic differentiation. Notably, one of the post‐transcriptional modifications of mRNA, namely, N 6 ‐methyladenosine (m 6 A), has been recently found to play a role in adipogenesis. Here, the roles of m 6 A‐related enzymes and proteins in adipogenesis, with a particular focus on how these m 6 A‐related proteins function at different stages of adipogenesis, are mainly discussed. The Review also highlights the coordination role of the transcriptional and post‐transcriptional (RNA m 6 A methylation) regulation in adipogenesis and related biological processes. In this context, a better understanding of adipogenesis at both the transcriptional and post‐transcriptional levels may facilitate the development of novel strategies to improve metabolic health in obesity.

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mRNA m6A methylation downregulates adipogenesis in porcine adipocytes

Cited by 102 publications

References 22 publications

Mouse Maternal High-Fat Intake Dynamically Programmed mRNA m6A Modifications in Adipose and Skeletal Muscle Tissues in Offspring

Mouse Maternal High-Fat Intake Dynamically Programmed mRNA m6A Modifications in Adipose and Skeletal Muscle Tissues in Offspring

A dynamic reversible RNA N⁶‐methyladenosine modification: current status and perspectives

Novel Insights into Adipogenesis from the Perspective of Transcriptional and RNA N6‐Methyladenosine‐Mediated Post‐Transcriptional Regulation

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mRNA m6A methylation downregulates adipogenesis in porcine adipocytes

Cited by 102 publications

References 22 publications

Mouse Maternal High-Fat Intake Dynamically Programmed mRNA m6A Modifications in Adipose and Skeletal Muscle Tissues in Offspring

Mouse Maternal High-Fat Intake Dynamically Programmed mRNA m6A Modifications in Adipose and Skeletal Muscle Tissues in Offspring

A dynamic reversible RNA N6‐methyladenosine modification: current status and perspectives

Novel Insights into Adipogenesis from the Perspective of Transcriptional and RNA N6‐Methyladenosine‐Mediated Post‐Transcriptional Regulation

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A dynamic reversible RNA N⁶‐methyladenosine modification: current status and perspectives