Search

Brown adipose tissue (BAT) is specialized to burn lipids for heat generation as a natural defense against cold and obesity. Previous studies established microRNAs (miRNAs) as essential regulators of brown adipocyte differentiation, but whether miRNAs are required for the feature maintenance of mature brown adipocytes remains unknown. To address this question, we ablated Dgcr8, a key regulator of the miRNA biogenesis pathway, in mature brown as well as in white adipocytes. Adipose tissue-specific Dgcr8 knockout mice displayed enlarged but pale interscapular brown fat with decreased expression of genes characteristic of brown fat and were intolerant to cold exposure. Primary brown adipocyte cultures in vitro confirmed that miRNAs are required for marker gene expression in mature brown adipocytes. We also demonstrated that miRNAs are essential for the browning of subcutaneous white adipocytes in vitro and in vivo. Using this animal model, we performed miRNA expression profiling analysis and identified a set of BAT-specific miRNAs that are upregulated during brown adipocyte differentiation and enriched in brown fat compared with other organs. We identified miR-182 and miR-203 as new regulators of brown adipocyte development. Taken together, our study demonstrates an essential role of miRNAs in the maintenance as well as in the differentiation of brown adipocytes. [ABSTRACT FROM AUTHOR]

Introduction: The clinical and echocardiographic correlates of atrial fibrillation (AF) among patients with heart failure and preserved versus reduced ejection fraction (HFpEF vs HFrEF) have not been not well studied in Asia. Hypothesis: There are regional differences in AF among Asian patients with HF. Methods: A total of 4541 patients with HFrEF (EF<40%) and 963 patients with HFpEF (EF≥50%) were enrolled from Northeast Asia (Korea, Japan, Taiwan, Hong Kong, and China), South Asia (India) and Southeast Asia (Thailand, Malaysia, Philippines, Indonesia, Singapore) in the prospective Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) study. AF was defined by history or baseline ECG. Outcomes (death or hospitalisation) were independently adjudicated. Results: Prevalence of AF was 22% in HFrEF (mean age 60±13, 78% male) and 38% in HFpEF (mean age 68±12, 47% male). Clinical correlates that differentially associated with AF in HFpEF vs HFrEF included age, region, and chronic kidney disease; whereas echocardiographic correlates that differentially associated with AF in HFpEF vs HFrEF included left atrial volume (Figure 1A). South Asians had the lowest prevalence of AF (6%, 12% in HFrEF, HFpEF) compared to Northeast Asians (39%, 49%) and Southeast Asians (21%, 37%)(p<0.001). Odds of AF were higher in Northeast Asians (adjusted OR 2.07, 95% CI 1.79-2.40) and lower in South Asians (adjusted OR 0.23, 95% CI 0.18-0.30) when compared to Southeast Asians. Differential odds of AF by region were mediated by both clinical and echocardiographic correlates (Figure 1B). There were striking differences in ethnic associations by region, where Indians from Southeast Asia had a higher odds of AF than Indians from South Asia (OR 2.49, 95% CI 1.68-3.70), and Chinese from Southeast Asia had lower odds of AF than Chinese from Northeast Asia (OR 0.80, 95% CI 0.66-0.98). AF increased the risk of the composite outcome of all-cause mortality and HF hospitalisations (adjusted OR 1.28, 95% CI 1.09-1.51), with similar prognostic impact in HFpEF and HFrEF (Pinteraction0.39). Conclusions: These findings highlight the regional differences in AF among Asian patients with HF. South Asians with HF have a strikingly low prevalence of AF, a difference deserving of further study. [ABSTRACT FROM AUTHOR]