High intensity exercise downregulates FTO mRNA expression during the early stages of recovery in young males and females

Danaher, Jessica; Stathis, Christos G.; Wilson, Robin A.; Moreno-Asso, Alba; Wellard, R. Mark; Cooke, Molly

doi:10.1186/s12986-020-00489-1

Cited by 8 publications

(4 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Depletion of m 6 A demethylase, FTO, led to impaired differentiation and fusion in vitro and impaired postnatal skeletal muscle development in vivo [ 21 ], and the overexpression of FTO promoted myoblast differentiation [ 22 ]. Similar to the results of our study, a dynamic pattern of FTO expression during myogenesis and different physiological processes in skeletal muscle has been observed [ 47 , 48 ]; however, the upstream regulation of this expression remains elusive. A recent study on FTO has shown that multiple metabolites can bind to FTO and regulate m 6 A levels [ 35 ].…”

Section: Discussionsupporting

confidence: 89%

DHA alleviates diet-induced skeletal muscle fiber remodeling via FTO/m6A/DDIT4/PGC1α signaling

Chen

et al. 2022

BMC Biol

View full text Add to dashboard Cite

Background Obesity leads to a decline in the exercise capacity of skeletal muscle, thereby reducing mobility and promoting obesity-associated health risks. Dietary intervention has been shown to be an important measure to regulate skeletal muscle function, and previous studies have demonstrated the beneficial effects of docosahexaenoic acid (DHA; 22:6 ω-3) on skeletal muscle function. At the molecular level, DHA and its metabolites were shown to be extensively involved in regulating epigenetic modifications, including DNA methylation, histone modifications, and small non-coding microRNAs. However, whether and how epigenetic modification of mRNA such as N6-methyladenosine (m6A) mediates DHA regulation of skeletal muscle function remains unknown. Here, we analyze the regulatory effect of DHA on skeletal muscle function and explore the involvement of m6A mRNA modifications in mediating such regulation. Results DHA supplement prevented HFD-induced decline in exercise capacity and conversion of muscle fiber types from slow to fast in mice. DHA-treated myoblasts display increased mitochondrial biogenesis, while slow muscle fiber formation was promoted through DHA-induced expression of PGC1α. Further analysis of the associated molecular mechanism revealed that DHA enhanced expression of the fat mass and obesity-associated gene (FTO), leading to reduced m6A levels of DNA damage-induced transcript 4 (Ddit4). Ddit4 mRNA with lower m6A marks could not be recognized and bound by the cytoplasmic m6A reader YTH domain family 2 (YTHDF2), thereby blocking the decay of Ddit4 mRNA. Accumulated Ddit4 mRNA levels accelerated its protein translation, and the consequential increased DDIT4 protein abundance promoted the expression of PGC1α, which finally elevated mitochondria biogenesis and slow muscle fiber formation. Conclusions DHA promotes mitochondrial biogenesis and skeletal muscle fiber remodeling via FTO/m6A/DDIT4/PGC1α signaling, protecting against obesity-induced decline in skeletal muscle function.

show abstract

Section: Discussionsupporting

confidence: 89%

DHA alleviates diet-induced skeletal muscle fiber remodeling via FTO/m6A/DDIT4/PGC1α signaling

Chen

et al. 2022

BMC Biol

View full text Add to dashboard Cite

show abstract

“…Our findings were also potentially interpreted by the epigenetic mechanisms possibly occurring during the intervention process. For example, individuals carrying the FTO risk allele might have a reduced risk of obesity after receiving physical activity interventions compared with those not receiving interventions, due to the downregulated expression of the FTO gene in skeletal muscle during the intervention process 50,51 . Take another instance, fruit‐based diets could downregulate the mRNA level of the FTO gene, 52 which might weaken the FTO –obesity association.…”

Section: Discussionmentioning

confidence: 99%

FTO genotype and body mass index reduction in childhood obesity interventions: A systematic review and meta‐analysis

Chen,

Xiao,

Zhao

et al. 2024

Obesity Reviews

View full text Add to dashboard Cite

SummaryNumerous guidelines have called for personalized interventions to address childhood obesity. The role of fat mass and obesity‐associated gene (FTO) in the risk of childhood obesity has been summarized. However, it remains unclear whether FTO could influence individual responses to obesity interventions, especially in children. To address this, we systematically reviewed 12,255 records across 10 databases/registers and included 13 lifestyle‐based obesity interventions (3980 children with overweight/obesity) reporting changes in body mass index (BMI) Z‐score, BMI, waist circumference, waist‐to‐hip ratio, and body fat percentage after interventions. These obesity‐related outcomes were first compared between children carrying different FTO genotypes (rs9939609 or its proxy) and then synthesized by random‐effect meta‐analysis models. The results from single‐group interventions showed no evidence of associations between FTO risk allele and changes in obesity‐related outcomes after interventions (e.g., BMI Z‐score: −0.01; 95% CI: −0.04, 0.01). The results from controlled trials showed that associations between the FTO risk allele and changes in obesity‐related outcomes did not differ by intervention/control group. To conclude, the FTO risk allele might play a minor role in the response to obesity interventions among children. Future studies might pay more attention to the accumulation effect of multiple genes in the intervention process among children.

show abstract

“…It is observed that males carrying the FTO risk allele lose more weight after a 12-week regular exercise [ 57 ]. An acute decreased skeletal muscle FTO mRNA expression was observed after high-intensity exercise by Danaher et al [ 14 ]. Most researchers focus on the reducing obesity risk caused by FTO gene polymorphisms under exercise, while there are few on its function.…”

Section: Discussionmentioning

confidence: 99%

“…FTO is highly expressed in the brain and likely involved in many nuclear RNA processing events, such as mRNA translation, splicing, and metabolism [ 11 , 13 ]. Previous study showed that highly intensive exercise decreases the skeletal muscle FTO mRNA [ 14 ]. However, the evidence on the effects of long-term exercise on FTO expression is scarce.…”

Section: Introductionmentioning

confidence: 99%

Long-term exercise training down-regulates m6A RNA demethylase FTO expression in the hippocampus and hypothalamus: an effective intervention for epigenetic modification

et al. 2022

View full text Add to dashboard Cite

Background Exercise boosts the health of some brain parts, such as the hippocampus and hypothalamus. Several studies show that long-term exercise improves spatial learning and memory, enhances hypothalamic leptin sensitivity, and regulates energy balance. However, the effect of exercise on the hippocampus and hypothalamus is not fully understood. The study aimed to find epigenetic modifications or changes in gene expression of the hippocampus and hypothalamus due to exercise. Methods Male C57BL/6 mice were randomly divided into sedentary and exercise groups. All mice in the exercise group were subjected to treadmill exercise 5 days per week for 1 h each day. After the 12-week exercise intervention, the hippocampus and hypothalamus tissue were used for RNA-sequencing or molecular biology experiments. Results In both groups, numerous differentially expressed genes of the hippocampus (up-regulated: 53, down-regulated: 49) and hypothalamus (up-regulated: 24, down-regulated: 40) were observed. In the exercise group, increased level of N6-methyladenosine (m6A) was observed in the hippocampus and hypothalamus (p < 0.05). Furthermore, the fat mass and obesity-associated gene (FTO) of the hippocampus and hypothalamus were down-regulated in the exercise group (p < 0.001). In addition, the Fto co-expression genes of the mouse brain were studied and analyzed using database to determine the potential roles of exercise-downregulated FTO in the brain. Conclusion The findings demonstrate that long-term exercise might elevates the levels of m6A-tagged transcripts in the hippocampus and hypothalamus via down-regulation of FTO. Hence, exercise might be an effective intervention for epigenetic modification.

show abstract

High intensity exercise downregulates FTO mRNA expression during the early stages of recovery in young males and females

Cited by 8 publications

References 41 publications

DHA alleviates diet-induced skeletal muscle fiber remodeling via FTO/m6A/DDIT4/PGC1α signaling

DHA alleviates diet-induced skeletal muscle fiber remodeling via FTO/m6A/DDIT4/PGC1α signaling

FTO genotype and body mass index reduction in childhood obesity interventions: A systematic review and meta‐analysis

Long-term exercise training down-regulates m6A RNA demethylase FTO expression in the hippocampus and hypothalamus: an effective intervention for epigenetic modification

Contact Info

Product

Resources

About