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CycloZ Improves Hyperglycemia and Lipid Metabolism by Modulating Lysine Acetylation in KK-Ay Mice
전종수,이도현,김보배,박보윤,오창주,김민지,전재한,이인규,Onyu Park,백서영,임채원,류동열,황성순,Johan Auwerx,Kyong-Tai Kim,Hoe-Yune Jung 대한당뇨병학회 2023 Diabetes and Metabolism Journal Vol.47 No.5
Background: CycloZ, a combination of cyclo-His-Pro and zinc, has anti-diabetic activity. However, its exact mode of action remains to be elucidated.Methods: KK-Ay mice, a type 2 diabetes mellitus (T2DM) model, were administered CycloZ either as a preventive intervention, or as a therapy. Glycemic control was evaluated using the oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) levels. Liver and visceral adipose tissues (VATs) were used for histological evaluation, gene expression analysis, and protein expression analysis.Results: CycloZ administration improved glycemic control in KK-Ay mice in both prophylactic and therapeutic studies. Lysine acetylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, liver kinase B1, and nuclear factor-κB p65 was decreased in the liver and VATs in CycloZ-treated mice. In addition, CycloZ treatment improved mitochondrial function, lipid oxidation, and inflammation in the liver and VATs of mice. CycloZ treatment also increased the level of β-nicotinamide adenine dinucleotide (NAD<sup>+</sup>), which affected the activity of deacetylases, such as sirtuin 1 (Sirt1).Conclusion: Our findings suggest that the beneficial effects of CycloZ on diabetes and obesity occur through increased NAD<sup>+</sup> synthesis, which modulates Sirt1 deacetylase activity in the liver and VATs. Given that the mode of action of an NAD+ booster or Sirt1 deacetylase activator is different from that of traditional T2DM drugs, CycloZ would be considered a novel therapeutic option for the treatment of T2DM.
Woo Hyun Cho,Hye Ju Yeo,Jeong Su Kim,Jin Ho Jang,Kipoong Kim,Sunghoon Park,Su Hwan Lee,Onyu Park,Taehwa Kim,Korean Intensive Care Study Group 대한결핵및호흡기학회 2024 Tuberculosis and Respiratory Diseases Vol.87 No.2
Background: Results of studies investigating the association between body mass index(BMI) and mortality in patients with coronavirus disease-2019 (COVID-19) have beenconflicting. Methods: This multicenter, retrospective observational study, conducted between January2020 and August 2021, evaluated the impact of obesity on outcomes in patientswith severe COVID-19 in a Korean national cohort. A total of 1,114 patients were enrolledfrom 22 tertiary referral hospitals or university-affiliated hospitals, of whom 1,099were included in the analysis, excluding 15 with unavailable height and weight information. The effect(s) of BMI on patients with severe COVID-19 were analyzed. Results: According to the World Health Organization BMI classification, 59 patientswere underweight, 541 were normal, 389 were overweight, and 110 were obese. Theoverall 28-day mortality rate was 15.3%, and there was no significant difference accordingto BMI. Univariate Cox analysis revealed that BMI was associated with 28-day mortality(hazard ratio, 0.96; p=0.045), but not in the multivariate analysis. Additionally, patientswere divided into two groups based on BMI ≥25 kg/m2 and underwent propensityscore matching analysis, in which the two groups exhibited no significant difference inmortality at 28 days. The median (interquartile range) clinical frailty scale score at dischargewas higher in nonobese patients (3 [3 to 5] vs. 4 [3 to 6], p<0.001). The proportionof frail patients at discharge was significantly higher in the nonobese group (28.1%vs. 46.8%, p<0.001). Conclusion: The obesity paradox was not evident in this cohort of patients with severeCOVID-19. However, functional outcomes at discharge were better in the obese group.