FTO in health and disease.

Fat mass and obesity-associated (FTO) protein, a key enzyme integral to the dynamic regulation of epitranscriptomic modifications in RNAs, significantly influences crucial RNA lifecycle processes, including splicing, export, decay, and translation. The role of FTO in altering the epitranscriptome manifests across a spectrum of physiological and pathological conditions. This review aims to consolidate current understanding regarding the implications of FTO in health and disease, with a special emphasis on its involvement in obesity and non-communicable diseases associated with obesity, such as diabetes, cardiovascular disease, and cancer.

Unveiling the proteome of the fasting heart: Insights into HIF-1 pathway regulation.

Fasting is a common dietary intervention known for its protective effects against metabolic and cardiovascular diseases. While its effects are mostly systemic, understanding tissue-specific changes in the heart is crucial for the identification of the mechanisms underlying fasting-induced cardioprotection. In this study, we performed a proteomic analysis of the fasting heart and attempted to clarify the molecular basis of fasting-induced cardioprotection.

HIF-1α limits myocardial infarction by promoting mitophagy in mouse hearts adapted to chronic hypoxia.

Aim: The transcriptional factor HIF-1α is recognized for its contribution to cardioprotection against acute ischemia/reperfusion injury. Adaptation to chronic hypoxia (CH) is known to stabilize HIF-1α and increase myocardial ischemic tolerance. However, the precise role of HIF-1α in mediating the protective effect remains incompletely understood.

Epitranscriptomic Regulations in the Heart.

RNA modifications affect key stages of the RNA life cycle, including splicing, export, decay, and translation. Epitranscriptomic regulations therefore significantly influence cellular physiology and pathophysiology. Here, we selected some of the most abundant modifications and reviewed their roles in the heart and in cardiovascular diseases: N6-methyladenosine (m6A), N6,2'-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), pseudouridine (?), 5 methylcytidine (m5C), and inosine (I).

Epitranscriptomic regulation in fasting hearts: implications for cardiac health.

Cardiac tolerance to ischaemia can be increased by dietary interventions such as fasting, which is associated with significant changes in myocardial gene expression. Among the possible mechanisms of how gene expression may be altered are epigenetic modifications of RNA - epitranscriptomics. N-methyladenosine (mA) and N,2'-O-dimethyladenosine (mAm) are two of the most prevalent modifications in mRNA.

The role of mA and mAm RNA modifications in the pathogenesis of diabetes mellitus.

The rapidly developing research field of epitranscriptomics has recently emerged into the spotlight of researchers due to its vast regulatory effects on gene expression and thereby cellular physiology and pathophysiology. N-methyladenosine (mA) and N,2'-O-dimethyladenosine (mAm) are among the most prevalent and well-characterized modified nucleosides in eukaryotic RNA. Both of these modifications are dynamically regulated by a complex set of epitranscriptomic regulators called writers, readers, and erasers.

RNA modification mAm: the role in cardiac biology.

Epitranscriptomic modifications have recently emerged into the spotlight of researchers due to their vast regulatory effects on gene expression and thereby cellular physiology and pathophysiology. N,2'-O-dimethyladenosine (mAm) is one of the most prevalent chemical marks on RNA and is dynamically regulated by writers (PCIF1, METTL4) and erasers (FTO). The presence or absence of mAm in RNA affects mRNA stability, regulates transcription, and modulates pre-mRNA splicing.

Myocardial m6A regulators in postnatal development: effect of sex.

N6-methyladenosine (m6A) is an abundant mRNA modification affecting mRNA stability and protein expression. It is a highly dynamic process, and its outcomes during postnatal heart development are poorly understood. Here we studied m6A machinery in the left ventricular (LV) myocardium of Fisher344 male and female rats (postnatal days one to ninety; P1-P90) using Western Blot.

Selection of optimal reference genes for gene expression studies in chronically hypoxic rat heart.

Adaptation to chronic hypoxia renders the heart more tolerant to ischemia/reperfusion injury. To evaluate changes in gene expression after adaptation to chronic hypoxia by RT-qPCR, it is essential to select suitable reference genes. In a chronically hypoxic rat model, no specific reference genes have been identified in the myocardium.

Infarct size-limiting effect of epoxyeicosatrienoic acid analog EET-B is mediated by hypoxia-inducible factor-1α via downregulation of prolyl hydroxylase 3.

Epoxyeicosatrienoic acids (EETs) decrease cardiac ischemia-reperfusion injury; however, the mechanism of their protective effect remains elusive. Here, we investigated the cardioprotective action of a novel EET analog, EET-B, in reperfusion and the role of hypoxia-inducible factor (HIF)-1α in such action of EET-B. Adult male rats were subjected to 30 min of left coronary artery occlusion followed by 2 h of reperfusion.

Myocardial ischemic tolerance in rats subjected to endurance exercise training during adaptation to chronic hypoxia.

Chronic hypoxia and exercise are natural stimuli that confer sustainable cardioprotection against ischemia-reperfusion (I/R) injury, but it is unknown whether they can act in synergy to enhance ischemic resistance. Inflammatory response mediated by tumor necrosis factor-α (TNF-α) plays a role in the infarct size limitation by continuous normobaric hypoxia (CNH), whereas exercise is associated with anti-inflammatory effects. This study was conducted to determine if exercise training performed under conditions of CNH (12% O) affects myocardial ischemic resistance with respect to inflammatory and redox status.

Detection of stress fractures in athletes and nonathletes.

Stress fractures are considered a relatively common athletic injury. Some authors also feel this disorder may be overlooked in many nonathletic patients. Three cases of stress fractures are presented.