Intermittent fasting (IF) plays an essential role in improving lipid metabolism disorders caused by metabolic cardiomyopathy. Growing evidence revealed that N6-methyladenosine (m6A) RNA methylation is related to obesity and lipid metabolic. Our study aimed to assess the beneficial effects of IF on lipid deposition, apoptosis, and m6A methylation in high-fat diet (HFD)-induced obesity cardiomyopathy. Male C57BL/6J mice were fed a normal diet (ND) or HFD ad libitum for 13 weeks, after which time a subgroup of HFD mice were subjected to IF for 24 h and fed HFD in the other day for 8 weeks. We found that IF intervention significantly improved cardiac functional and structural impairment and serum lipid metabolic disorder induced by HFD. Furthermore, IF intervention decreased the mRNA levels of the fatty acid uptake genes of FABP1, FATP1, and CD36 and the fatty acid synthesis genes of SREBF1, FAS, and ACCα and increased the mRNA levels of the fatty acid catabolism genes of ATGL, HSL, LAL, and LPL in cardiac tissueof HFD-induced obese mice. TUNEL-positive cells, Bax/Bcl-2 ratio, and Cleaved Caspase-3 protein expression in HFD-induced obese mice hearts was down-regulated by IF intervention. In addition, IF intervention decreased the m6A methylation levels and METTL3 expression and increased FTO expression in HFD-induced obesity cardiomyopathy. In conclusion, our findings demonstrate that IF attenuated cardiac lipid deposition and apoptosis, as well as improved cardiac functional and structural impairment in HFD-induced obesity cardiomyopathy, by a mechanism associated with decreased m6A RNA methylation levels.

Cardiometabolic diseases (CMDs) are currently the leading cause of death and disability worldwide, and their underlying regulatory mechanisms remain largely unknown. N6-methyladenosine (m6A) methylation, the most common and abundant epigenetic modification of eukaryotic mRNA, is regulated by m6A methyltransferase, demethylase, and the m6A binding protein, which affect the transcription, cleavage, translation, and degradation of target mRNA. m6A methylation plays a vital role in the physiological and pathological processes of CMDs. In this review, we summarize the role played by m6A methylation in CMDs, including obesity, hypertension, pulmonary hypertension, ischemic heart disease, myocardial hypertrophy, heart failure, and atherosclerosis. We also describe mechanisms that potentially involve the participation of m6A methylation, such as those driving calcium homeostasis, circadian rhythm, lipid metabolism, autophagy, macrophage response, and inflammation. m6A methylation and its regulators are expected to be targets for the treatment of CMDs.

Exercise could alleviate non-alcoholic fatty liver disease (NAFLD), but it was not clear which exercise methods could effectively treat NAFLD. The purpose of this systematic review and meta-analysis was to evaluate the effects of different exercise patterns on eight indicators in patients with NAFLD. We searched PubMed, Scopus, Web of Science, China National Knowledge Infrastructure, and the Wanfang Data from its inception to 30 June 2020. This review includes all randomized controlled trials (RCT) that assessed and compared the effects of different exercise on eight indicator parameters in patients with NAFLD. The results indicate that aerobic exercises could significantly improve the eight indicators in patients with NAFLD including triglycerides (TG, weighted mean difference (WMD) = −0.53, 95%CI: −0.68~−0.39, Z = 7.37, p < 0.01), total cholesterol (TC, WMD = −0.39, 95%CI: −0.55~−0.23, Z = 4.76, p < 0.01), low density lipoprotein (LDL, WMD = −0.47, 95%CI: −0.68~−0.26, Z = 4.33, p < 0.01), high density lipoprotein (HDL, WMD = 0.12, 95%CI: 0.05~0.18, Z = 3.56, p < 0.01), alanine aminotransferase (ALT, WMD = −6.14, 95%CI: −10.99~−1.29, Z = 2.48, p < 0.05), aspartate aminotransferase (AST, WMD = −5.73, 95%CI: −9.08~−2.38, Z = 3.36, p < 0.01), and body mass index (BMI, WMD = −0.85, 95%CI: −1.19~−0.51, Z = 4.92, p < 0.01). Resistance exercises could significantly reduce the levels of TG (WMD = −0.56, 95%CI: −0.85~−0.28, Z = 3.86, p < 0.01) and AST (WMD = −2.58, 95%CI: −4.79~−0.36, Z = 2.28, p < 0.05) in the patients. High-intensity interval training could significantly improve the level of ALT (WMD = −6.20, 95%CI: −9.34~−3.06, Z = 3.87, p < 0.01) in patients with NAFLD. These three exercise methods had different effects on the eight indexes of NAFLD in our present meta-analysis, providing some reference for the establishment of exercise prescription for patients with NAFLD.

Exercise is an effective way to improve reproductive function in obese males. Oxidative stress and apoptosis are important pathological factors of obesity-related male infertility. Accumulating studies have demonstrated that N6-methyladenosine (m6A) methylation is associated with obesity and testicular reproductive function. Our study aimed to investigate and compare the effect of 8 weeks of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on testicular oxidative stress, apoptosis and m6A methylation in obese male mice. Male C57BL/6 mice were randomly allocated into the four groups: normal diet (ND) group, high-fat diet (HFD) group, high-fat diet with moderate-intensity continuous training (HFD-MICT) group and high-fat diet with high-intensity interval training (HFD-HIIT) group. Mice in the HFD-MICT and HFD-HIIT groups were subjected to 8 weeks of MICT or HIIT treadmill protocols after 12 weeks of HFD feeding. We found that MICT and HIIT increased the protein expression of Nrf2, HO-1 and NQO-1 in the testes of obese mice, and HIIT increased it more than MICT. The Bax/Bcl-2 ratio, Cleaved Caspase-3 protein expression and TUNEL-positive cells were consistently up-regulated in the testes of obese mice, but MICT and HIIT restrained these HFD-induced effects. In addition, HFDs increased m6A levels and the gene expression of METTL3, YTHDF2 and FTO in the testes, but these effects were reversed by MICT and HIIT. However, HIIT was more effective than MICT in reducing m6A methylation in the testes of obese mice. These results demonstrate that both MICT and HIIT protected against HFD-induced oxidative stress, apoptosis and m6A methylation in testicular tissues; as a result, testicular morphological and functional impairment improved. In particular, HIIT was more beneficial than MICT in increasing the mRNA expression of steroidogenic enzymes and testicular antioxidant capacity and decreasing m6A methylation in the testes of HFD-fed mice.

Type 2 diabetes mellitus (T2DM) is a metabolic disease primarily characterized by insulin resistance (IR) and insufficient insulin secretion. The unfolded protein response (UPR) overactivation induced by endoplasmic reticulum stress (ERS) appears to play a key role in this process, although the exact pathogenesis of T2DM is not fully understood. Studies have demonstrated that appropriate exercise can regulate ERS in the heart, liver, pancreas, skeletal muscle, and other body tissues leading to an improvement in diabetes and its complications. However, the exact mechanism remains unclear. By analyzing the relationship between ERS, T2DM pathology, and exercise intervention, this review concludes that exercise can increase insulin sensitivity, inhibit IR, promote insulin secretion and alleviate T2DM by regulating ERS. This paper specifically reviews the signaling pathways by which ERS induces diabetes, the mechanisms of exercise regulation of ERS in diabetes, and the varying effects of different types of exercise on diabetes improvement through ERS mechanisms. Physical exercise is an effective non-pharmacological intervention for T2DM. Thus, further exploration of how exercise regulates ERS in diabetes could refine "precision exercise medicine" for diabetes and identify new drug targets.