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Dihydromyricetin (DHM) is a natural bioactive flavonoid extracted from Ampelopsis Grossedentata , a commonly used Chinese herbal medicine. It has multiple beneficial pharmacological effects including lowering blood glucose and lipid, as well as anti-inflammation, anti-oxidation and hepato-protection. In this study, we elucidated its actions on mitochondrial dynamics and browning of white adipose. In the experiments in vivo , six-week-old male C57BL/6 mice were fed with normal diet (ND), high-fat diet (HFD), or HFD with intragastric administration of DHM (250 mg/kg.d−1); in the experiments in vitro , 3T3-L1 and mouse primary preadipocytes were induced and treated with various concentrations of DHM. The mouse metabolic phenotype, lipid accumulation, the browning and mitochondrial dynamics of white adipocytes were examined. It was found that DHM treatment reduced body weight and fat mass, improved glucose tolerance, insulin resistance and cold tolerance in mice with obesity. DHM treatment increased the expressions of classical brown adipocyte markers (UCP-1, PGC-1α, PRDM16) and mitochondrial dynamics-related proteins (DRP1, FIS1, OPA1, MFN2) in adipose tissue. Likewise, DHM treatment induced the differentiation of mature 3T3-L1 cells into brown-like adipocytes and also enhanced the expressions of mitochondrial dynamics-related proteins in vitro. Moreover, the pro-browning effect of DHM can be abrogated by mitochondrial fission inhibitor Mdivi-1. These findings indicate that DHM treatment induces the browning-remodeling of white adipose by enhancing mitochondrial fission and manifests an anti-obesity property via pro-browning mediated by mitochondrial fission, which implies it may play important roles in prevention and therapy of obesity and related diseases. [Display omitted] • DHM reduces body weights and fat accumulation, improves the homeostasis of glycolipid metabolism and insulin resistance. • DHM promotes the browning of WAT both in vitro and in vivo. • DHM induces the browning-remodeling of WAT by enhancing the mitochondrial fission. [ABSTRACT FROM AUTHOR]

The necessity and efficacy of statin treatment for abdominal aortic aneurysm (AAA) remains controversial. This systematic review and meta-analysis was conducted to investigate the effects of statin therapy on the outcomes of patients with AAA. The Cochrane library, Embase, and MedLine were searched comprehensively to identify relevant cohort studies and randomized controlled trials. The primary outcomes included short- and long-term mortality after AAA repair, and secondary outcomes included the incidence of perioperative cardiovascular complications, sac shrinkage after endovascular aneurysm repair, and the growth rate of the aneurysms. Short-term mortality was defined as all-cause 30-day or in-hospital postoperative mortality. Long-term mortality was defined as the all-cause mortality at the end of follow-up period (≥1 year). A random effects model was used to combine the results of included studies. Forest plots were created to show the pooled results of each outcome. One post hoc analysis of a randomized trial and 36 cohort studies (n = 134,290 patients) were included in this systematic review. The average score of included studies by Newcastle-Ottawa Scale was 7.76. Patients taking or not taking statin therapy were all diagnosed with unruptured AAA, and 59.9% of these patients were given statin therapy. Compared with statin nonusers, patients in statin therapy had significantly lower long-term mortality (odds ratio, 0.67; 95% confidence interval, 0.59-0.75; P <.001; I2 = 71.7%), and short-term mortality after aneurysmal repair (odds ratio, 0.51; 95% confidence interval, 0.36-0.73; P <.001; I2 = 81.4%). No significant difference was found between patients taking or not taking statin treatment on perioperative cardiovascular complications or sac shrinkage after endovascular aneurysm repair or growth rate of AAA under surveillance. These findings suggest that statin use is associated with a significant decrease in long- and short-term mortality in patients after AAA repair. Based on these results, statin therapy is worth being used in clinical practice for the management of AAA. [ABSTRACT FROM AUTHOR]

• Increased vascular tones were observed in both diabetic patients and animals. • GLP-1 supplementation improved the mitochondrial functions and vascular tones. • GLP-1 supplementation enhanced adiponectin, AMPK and Sirt1 expressions. • CREB phosphorylation was enhanced by GLP-1 and promoted adiponectin transcription. The dysfunction of vasculature is observed in diabetes and might be responsible for the increased incidence of vascular events. Previous studies indicated that supplementation of GLP-1 analogues is beneficial to the cardiovascular functions in diabetic patients, but the mechanisms are not clear. A type 1 diabetic model was constructed. Vascular constrictions were measured using wire myograph. Western blotting and quantitative PCR were adopted to analyze the expression profiles of key molecules. Mitochondrial functions were analyzed in both vascular tissues or vascular smooth muscle cells (VSMCs). Dual-luciferase reporter assay was used to investigate the mechanism of adiponectin regulation. In this study, abnormal vascular hypertrophy and increased vascular tones were observed in both diabetic patients and animals. ROS productions were increased in vessels and VSMCs from diabetic patients and animals, and the ROS scavenger mitoTEMPO partially attenuated the abnormal vascular tones and hypertension. In addition, decreased GLP-1 levels were observed, while GLP-1 supplementation improved the mitochondrial functions and vascular tones. Furthermore, it was shown that GLP-1 supplementation enhanced adiponectin expressions, while adiponectin facilitated the phosphorylation of AMPK and Sirt1 expressions. Also, CREB phosphorylation was enhanced upon GLP-1 supplementation and promoted the transcriptions of adiponectin. Finally, CREB inhibition partially attenuated the effects of GLP-1 on mitochondrial functions and adiponectin expressions. GLP-1 downregulation might be an important mechanism of abnormal mitochondrial function and vascular tone in diabetes. Targeting GLP-1/CREB/adiponectin axis might become a promising therapeutic strategy in alleviating diabetes-related cardiovascular dysfunctions. [ABSTRACT FROM AUTHOR]

PPARγ1 and FOXO1 are the key transcription factors that regulate insulin sensitivity. We previously found that a small ubiquitin-related modifier of PPARγ1 at K77 (SUMOylation) favored endothelial insulin resistance (IR) induced by high fat/high glucose (HF/HG) administration. However, whether and how the crosstalk between SUMOylated PPARγ1 and FOXO1 would mediate the development of the endothelial IR and dysfunction remains unclear. Here, we emphasize how PPARγ1-K77 SUMOylation would interact with FOXO1 and participate in the development of the endothelial IR and dysfunction. Our results show that the combination of HF/HG and PPARγ1-K77 SUMOylation exhibits a synergistic deteriorative effect on the endothelial IR and dysfunction, presenting decreased NO levels and elevated ET-1 levels, weakened PI3K/Akt/eNOS signaling, and impaired endothelium-dependent vasodilation function. The further researches reveal that PPARγ1-K77 SUMOylation readily interacts with FOXO1, and FOXO1 occupies the PPAR response element (PPRE) which is supposed to be occupied by PPARγ, thus resulting in the decrease of PPARγ1 transcription activity and the mitigation of the PI3K/Akt signaling. Moreover, the mitigation of the PI3K/Akt signaling promotes in turn the accumulation of FOXO1 in the nucleus where FOXO1 interacts with the SUMOylated PPARγ1, thus exerting a positive feedback effect on IR pathogenesis. The findings uncover a novel association between PPARγ1-K77 SUMOylation and FOXO1, which contributes to our understanding of the pathogenesis of endothelial IR and dysfunction and provides novel pharmacological targets for diabetic angiopathy. [Display omitted] • PPARγ1-K77 SUMOylation combined with HF/HG exhibits a synergistic deteriorative effect on the endothelial IR and dysfunction. • PPARγ1-K77 SUMOylation impairs rats endothelium-dependent vasodilation. • FOXO1 blocks the PPRE binding site on PI3K and represses the PPARγ transcription activity via PPARγ1-K77 SUMOylation. • PPARγ1-K77 SUMOylation causes FOXO1 nuclear accumulation by negatively regulating FOXO1 phosphorylation via PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]

As a flavonoid, naringin (Nar) has been shown to have multiple pharmacological effects including lowering blood cholesterol, reducing thrombus formation and improving microcirculation. However, effects of Nar on function and autophagy of vascular endothelial cells under high glucose and high fat (HG/HF) stress are largely unclear. This study was designed to investigate such effects of Nar in human umbilical vein endothelial cells (HUVECs) and to determine whether such effects are related to autophagy. Our present results show that 86 μM of Nar inhibits the autophagy levels and protects the cells against the dysfunction induced by HG/HF stress. Moreover, Nar increases the phosphorylation levels of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt) and mammalian rapamycin target protein (mTOR). However, pretreatment with rapamycin (RAPA, 5 μM, autophagy inducer), LY294002(10 μM, PI3K inhibitor) and Akt inhibitor Ⅳ (0.5 μM, Akt inhibitor) partially abrogates the protective effects of Nar, suggesting that the protective effects of Nar are achieved by activating the PI3K-Akt-mTOR pathway to inhibit autophagy. In conclusion, Nar improves the function of HUVECs under HG/HF stress through activating the PI3K-Akt-mTOR pathway to inhibit autophagy. The findings offer an insight into HG/HF stress-induced autophagy and indicate that Nar might have potential to prevent and treat the diabetic angiopathy. Image 1 [ABSTRACT FROM AUTHOR]