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Growing evidence suggests an independent relationship between habitual snoring and metabolic abnormalities. Currently, there are few data available on the association between snoring and hyperuricemia. Therefore, we evaluated the cross-sectional association between snoring and serum uric acid (UA) concentration and ascertain the effects of different snoring intensities on hyperuricemia among Chinese urban adults in Nanjing.We performed a cross-sectional study including 7699 participants (4197 men and 3502 women) from Nanjing Drum Tower Hospital aged ≥18 years over a two year (ie, 2016-2018) period. All participants were divided into four groups based on Snoring scores. Questionnaires, physical examinations and biochemical tests were conducted. Hyperuricemia was defined as levels of serum UA6.8 mg/dL in males and6.0 mg/dL in females. We used a generalized linear model to investigate the association between snoring and serum UA concentration and logistic regression model to investigate the association between snoring and likelihood of having hyperuricemia in the age-, sex-adjusted model and in a multivariable model adjusting for demographic factor, plasma lipid profiles, blood glucose, blood pressure, smoking, and alcohol consumption.The prevalence of hyperuricemia was 10.05% in the studied population and gradually increased across the snoring scores (P 0.0001). We found that mild snoring, moderate, and severe snoring intensity were associated with high serum UA in the age-, sex-adjusted model and in a multivariable model adjusting for demographic and lifestyle/behavioral risk factors. The association was insisted with the addition of variables related to clinical outcomes such as diabetes, hypertension, and high-cholesterol levels.Our results showed self-reported habitual snoring was associated with higher serum UA concentration among Chinese urban adults. Findings of this study indicate the significance of early detection and treatment of snoring to prevent hyperuricemia.

Overconsumption of sugar-sweetened beverages (SSBs) is associated with an increased risk of metabolic disorders, including obesity and diabetes. However, accumulating evidence also suggests the potential negative impact of consuming nonnutritive sweeteners (NNSs) on weight and glycaemic control. The metabolic effects of sucralose, the most widely used NNS, remain controversial. This study aimed to compare the impact of intake of dietary sucralose (acceptable daily intake dose, ADI dose) and sucrose-sweetened water (at the same sweetness level) on lipid and glucose metabolism in male mice.Sucralose (0.1 mg/mL) or sucrose (60 mg/mL) was added to the drinking water of 8-week-old male C57BL/6 mice for 16 weeks, followed by oral glucose and intraperitoneal insulin tolerance tests, and measurements of bone mineral density, plasma lipids, and hormones. After the mice were sacrificed, the duodenum and ileum were used for examination of sweet taste receptors (STRs) and glucose transporters.A significant increase in fat mass was observed in the sucrose group of mice after 16 weeks of sweetened water drinking. Sucrose consumption also led to increased levels of plasma LDL, insulin, lipid deposition in the liver, and increased glucose intolerance in mice. Compared with the sucrose group, mice consuming sucralose showed much lower fat accumulation, hyperlipidaemia, liver steatosis, and glucose intolerance. In addition, the daily dose of sucralose only had a moderate effect on T1R2/3 in the intestine, without affecting glucose transporters and plasma insulin levels.Compared with mice consuming sucrose-sweetened water, daily drinking of sucralose within the ADI dose had a much lower impact on glucose and lipid homeostasis.

Rationale: Targeting vascular smooth muscle cell (VSMC) phenotypic switching is a promising therapeutic approach for atherosclerosis. Dysregulation of PGC1α (peroxisome proliferator-activated receptor gamma, coactivator 1α), a key regulator of cellular energy metabolism, has been implicated in the pathogenesis of atherosclerosis, yet its role in atherosclerosis remains controversial. Objective: The current study aimed to determine whether and how PGC1α in VSMCs regulates atherosclerosis progression. Methods and Results: We generated transgenic rabbits with SMC-specific PGC1α overexpression and showed that these rabbits developed significantly less aortic atherosclerosis than their nontransgenic littermates after high-cholesterol diet feeding, while total plasma cholesterol levels were similar. As indicated by the restored expression of VSMC differentiation marker genes, the high-cholesterol diet-induced phenotypic switching in the aortic media was largely reversed in transgenic rabbits, accompanied by decreased levels of synthetic phenotype genes, proinflammatory cytokines, adhesion molecules, macrophage infiltration, MMPs (matrix metalloproteinases), reactive oxygen species production and senescence. Ex vivo studies further showed that VSMC-specific PGC1α overexpression markedly suppressed the promotive effect of high-cholesterol diet feeding on the association of SRF (serum response factor) with ELK1 (ETS transcription factor ELK1), a TCF (ternary complex factor) that acts as a myogenic repressor in VSMCs, thereby preserving the VSMC contractile phenotype. Furthermore, knockdown of PGC1α remarkably increased ERK (extracellular signal-regulated kinase)1/2-ELK-1 signaling, which promoted phenotypic switching and proliferation of cultured rabbit VSMCs. In addition, we showed that PGC1α can regulate EGFR (epidermal growth factor receptor)-ERK1/2 MAPK (mitogen-activated protein kinase) signaling via modulating PPARγ (peroxisome proliferator-activated receptor γ) activity in RVSMCs (rabbit vascular smooth muscle cells). Finally, we showed that these beneficial results of SMC-specific PGC1α overexpression can be extrapolated from rabbits to human VSMCs and clinical settings. Conclusions: We demonstrated a critical role of PGC1α in maintaining the contractile phenotype of VSMCs and highlighted the therapeutic potential of PGC1α for atherosclerosis.

The global rise in obesity has become a public health crisis. During the onset of obesity, disrupted catecholamine signals have been described to contribute to excess fat accumulation, however, the molecular and metabolic change of subcutaneous adipose tissue (SAT) upon chronic high-fat feeding has rarely been investigated. Here, we show that chronic high-fat feeding caused a significant decrease in the expression of thermogenic genes and acquisition of partial deleterious features of visceral fat in SAT. Upregulated miR-149-3p was involved in this obesity-induced “visceralization” of SAT via inhibiting PRDM16, a master regulator that promoted SAT thermogenesis. Reduction of miR-149-3p significantly increased PRDM16 expression in SAT, with improved whole-body insulin sensitivity, decreased SAT inflammation, and liver steatosis in high-fat fed mice. These findings provided direct evidence of the anti-obese and anti-diabetic effect of PRDM16 in the obese background for the first time and identified that miR-149-3p could serve as a therapeutic target to protect against diet-induced obesity and metabolic dysfunctions. Keywords: diet-induced obesity, miR-149-3p, Prdm16, subcutaneous adipose tissue, thermogenesis