Sun X. Irisin improves endothelial function in obese mice through the AMPK-eNOS pathway. Am J Physiol Heart Circ Physiol 309: H1501-H1508, 2015. First published September 14, 2015 doi:10.1152/ajpheart.00443.2015.-Irisin is a novel hormone secreted by myocytes. Lower levels of irisin are independently associated with endothelial dysfunction in obese subjects. The objective of this study was to explore whether irisin exerts a direct vascular protective effect on endothelial function in high-fat-diet-induced obese mice. Male C57BL/6 mice were given chow or a high-fat diet with or without treatment with irisin. Aortic endothelial function was determined by measuring endothelium-dependent vasodilatation (EDV). Nitric oxide (NO) in the aorta was determined. The effect of irisin on the levels of AMP-activated protein kinase (AMPK), Akt, and endothelial NO synthase (eNOS) phosphorylation in endothelial cells was determined. Human umbilical vein endothelial cells were used to study the role of irisin in the AMPK-eNOS pathway. Acetylcholine-stimulated EDV was significantly lower in obese mice compared with control mice. Treatment of obese mice with irisin significantly enhanced EDV and improved endothelial function. This beneficial effect of irisin was partly attenuated in the presence of inhibitors of AMPK, Akt, and eNOS. Treatment of obese mice with irisin enhanced NO production and phosphorylation of AMPK, Akt, and eNOS in endothelial cells. These factors were also enhanced by irisin in human umbilical vein endothelial cells in vitro. Suppression of AMPK expression by small interfering RNA blocked irisin-induced eNOS and Akt phosphorylation and NO production. We have provided the first evidence that irisin improves endothelial function in aortas of high-fat-diet-induced obese mice. The mechanism for this protective effect is related to the activation of the AMPK-eNOS signaling pathway. irisin; endothelial function; nitric oxide; obesity NEW & NOTEWORTHYIrisin improved endothelial function in aortas of high-fat-dietinduced obese mice. The mechanism for the protective effect of irisin is related to activation of the AMP-activated protein kinase-endothelial nitric oxide synthase signaling pathway.

AimsWe conducted a systematic review and meta-analysis to assess various antidiabetic agents’ association with mortality in patients with type 2 diabetes (T2DM) who have coronavirus disease 2019 (COVID-19).MethodsWe performed comprehensive literature retrieval from the date of inception until February 2, 2021, in medical databases (PubMed, Web of Science, Embase, and Cochrane Library), regarding mortality outcomes in patients with T2DM who have COVID-19. Pooled OR and 95% CI data were used to assess relationships between antidiabetic agents and mortality.ResultsEighteen studies with 17,338 patients were included in the meta-analysis. Metformin (pooled OR, 0.69; P=0.001) and sulfonylurea (pooled OR, 0.80; P=0.016) were associated with lower mortality risk in patients with T2DM who had COVID-19. However, patients with T2DM who had COVID-19 and received insulin exhibited greater mortality (pooled OR, 2.20; P=0.002). Mortality did not significantly differ (pooled OR, 0.72; P=0.057) between DPP-4 inhibitor users and non-users.ConclusionsMetformin and sulfonylurea could be associated with reduced mortality risk in patients with T2DM who have COVID-19. Furthermore, insulin use could be associated with greater mortality, while DPP-4 inhibitor use could not be. The effects of antidiabetic agents in patients with T2DM who have COVID-19 require further exploration.Systematic Review RegistrationPROSPERO (identifier, CRD42021242898).

BackgroundWith the increase in the aging population worldwide, Alzheimer's disease has become a rapidly increasing public health concern. Monitoring the dementia disease burden will support health development strategies by providing scientific data.MethodsBased on the data obtained from the 2019 Global Burden of Disease (GBD) database, the numbers and age-standardized rates (ASRs) of incidence, prevalence, death, and disability-adjusted life-years (DALYs) of Alzheimer's disease and other dementias from 1990 to 2019 were analyzed. Calculated estimated annual percentage changes (EAPCs) and Joinpoint regression analyses were performed to evaluate the trends during this period. We also evaluated the correlations between the epidemiology and the sociodemographic index (SDI), an indicator to evaluate the level of social development in a country or region considering the education rate, economic situation, and total fertility rate.ResultsFrom 1990 to 2019, the incidence and prevalence of Alzheimer's disease and other dementias increased by 147.95 and 160.84%, respectively. The ASR of incidence, prevalence, death, and DALYs in both men and women consistently increased over the study period. All the ASRs in women were consistently higher than those in men, but the increases were more pronounced in men. In addition, the ASRs of incidence, prevalence, and DALYs were positively correlated with the SDI. Moreover, the proportion of patients over 70 years old with dementia was also positively correlated with the SDI level. Smoking was a major risk factor for the disease burden of dementia in men, while obesity was the major risk factor for women.ConclusionFrom 1990 to 2019, the Alzheimer's disease burden increased worldwide. This trend was more serious in high-SDI areas, especially among elderly populations in high-SDI areas, who should receive additional attention. Policy-makers should take steps to reverse this situation. Notably, women were at a higher risk for the disease, but the risk in men showed a faster increase. We should give attention to the aging population, attach importance to interventions targeting dementia risk factors, and formulate action plans to address the increasing incidence of dementia.

Circulating irisin level was decreased in nonhypertensive, nondiabetic obese subjects compared with lean healthy control. Lower levels of irisin are independently associated with endothelial dysfunction. Therefore, irisin may be involved in the regulation of endothelial function in obesity.

BackgroundPolycystic ovary syndrome (PCOS), whose etiology remains uncertain, is a highly heterogenous and genetically complex endocrine disorder. The aim of this study was to identify differentially expressed genes (DEGs) in granulosa cells (GCs) from PCOS patients and make epigenetic insights into the pathogenesis of PCOS.ResultsIncluded in this study were 110 women with PCOS and 119 women with normal ovulatory cycles undergoing in vitro fertilization acting as the control group. RNA-seq identified 92 DEGs unique to PCOS GCs in comparison with the control group. Bioinformatic analysis indicated that synthesis of lipids and steroids was activated in PCOS GCs. 5-Methylcytosine analysis demonstrated that there was an approximate 25% reduction in global DNA methylation of GCs in PCOS women (4.44 ± 0.65%) compared with the controls (6.07 ± 0.72%; P < 0.05). Using MassArray EpiTYPER quantitative DNA methylation analysis, we also found hypomethylation of several gene promoters related to lipid and steroid synthesis, which might result in the aberrant expression of these genes.ConclusionsOur results suggest that hypomethylated genes related to the synthesis of lipid and steroid may dysregulate expression of these genes and promote synthesis of steroid hormones including androgen, which could partially explain mechanisms of hyperandrogenism in PCOS.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0442-y) contains supplementary material, which is available to authorized users.