No abstract

White adipose tissue (WAT) is important for maintenance of homeostasis, because it stores energy and secretes adipokines. The WAT of obese people demonstrates mitochondrial dysfunction, accompanied by oxidative stress, which leads to insulin resistance. WW domain‐containing E3 ubiquitin protein ligase 1 (WWP1) is a member of the HECT‐type E3 family of ubiquitin ligases and is associated with several diseases. Recently, we demonstrated that WWP1 is induced specifically in the WAT of obese mice, where it protects against oxidative stress. Here, we investigated the function of WWP1 in WAT of obese mice by analyzing the phenotype of Wwp1 knockout (KO) mice fed a high‐fat diet. The levels of oxidative stress markers were higher in obese WAT from Wwp1 KO mice. Moreover, Wwp1 KO mice had lower activity of citrate synthase, a mitochondrial enzyme. We also measured AKT phosphorylation in obese WAT and found lower levels in Wwp1 KO mice. However, plasma insulin level was low and glucose level was unchanged in obese Wwp1 KO mice. Moreover, both glucose tolerance test and insulin tolerance test were improved in obese Wwp1 KO mice. These findings indicate that WWP1 participates in the antioxidative response and mitochondrial function in WAT, but knockdown of WWP1 improves whole‐body glucose metabolism.

Aims The CONtrolling NUTritional status (CONUT) score represents the nutritional status of patients with heart failure (HF). Although high CONUT scores on admission are associated with increased risks of cardiovascular (CV) events in patients with HF, the impact of CONUT changes during hospitalization on their long‐term prognosis is unclear. This study aimed to investigate the impact of CONUT score changes on the clinical outcomes of patients with HF after discharge. Methods and results This observational study included 1705 patients hospitalized with HF who were discharged alive. The patients were categorized depending on their CONUT scores at admission and discharge into persistently high, high at admission and normal at discharge, normal at admission and high at discharge, and persistently normal CONUT groups. The primary endpoint was a composite of CV death and readmission for HF after discharge. The primary endpoint occurred in 652 patients (38%) during the median 525 day follow‐up period. Patients with persistently high CONUT scores had the highest composite endpoint rate (log‐rank trend test: P < 0.001). After adjusting for covariates, the hazard ratio for the composite outcome was significantly lower for the patients with high CONUT scores at admission and normal CONUT scores at discharge than that for those with persistently high CONUT scores (hazard ratio: 0.69; 95% confidence interval: 0.49–0.98). Conclusions Nutritional status changes in patients with HF that occurred during hospitalization were associated with CV events after discharge. Improving the nutritional status of patients may improve their clinical outcomes.

There is limited data on whether diastolic dysfunction in patients with heart failure (HF) and recovered ejection fraction (HFrecEF) is associated with worse prognosis. We retrospectively assessed 96 patients diagnosed with HFrecEF and created ROC curve of their diastolic function at the 1-year follow-up for the composite endpoint of cardiovascular death and HF readmission after the follow-up. Eligible patients were divided into two groups according to the cutoff value of E/e′ ratio (12.1) with the highest AUC (0.70). Kaplan–Meier analysis showed that HFrecEF with high E/e′ group had a significantly poorer prognosis than the low E/e′ group (log-rank, p = 0.01). Multivariate Cox regression analysis revealed that the high E/e′ group was significantly related to the composite endpoint (hazard ratio 5.45, 95% confidence interval [CI] 1.23–24.1). The independent predictors at discharge for high E/e′ ratio at the 1-year follow-up were older age and female sex after adjustment for covariates (odds ratio [OR] 1.07, 95% CI 1.01–1.13 and OR 4.70, 95% CI 1.08–20.5). In conclusion, HFrecEF with high E/e′ ratio might be associated with a poor prognosis. Older age and female sex were independent predictors for a sustained high E/e′ ratio in patients with HFrecEF.

A strategy using Alicyclobacillus F-62 glutaminase was established to minimize the nonenzymatic production acid was influenced by pH and temperature, and decreased over a pH range of 4-6 at 30C. Under optimum conditions (30C and pH 5.0), the L-glutamic and L-pyroglutamic acids obtained from 1 mM L-glutamine in the presence of glutaminase from Alicyclobacillus F-62 were 0.96 and 0.03 mM, respectively. This novel method is useful for the efficient production of L-glutamic acid during food-protein processing. 4 Corresponding