Hepatic steatosis is frequently observed in obese and aged individuals. Because hepatic steatosis is closely associated with metabolic syndromes, including insulin resistance, dyslipidemia, and inflammation, numerous efforts have been made to develop compounds that ameliorate it. Here, a novel peroxisome proliferator-activated receptor (PPAR) α agonist, 4-(benzo[d]thiazol-2-yl)benzene-1,3-diol (MHY553) was developed, and investigated its beneficial effects on hepatic steatosis using young and old Sprague-Dawley rats and HepG2 cells.Docking simulation and Western blotting confirmed that the activity of PPARα, but not that of the other PPAR subtypes, was increased by MHY553 treatment. When administered orally, MHY553 markedly ameliorated aging-induced hepatic steatosis without changes in body weight and serum levels of liver injury markers. Consistent with in vivo results, MHY553 inhibited triglyceride accumulation induced by a liver X receptor agonist in HepG2 cells. Regarding underlying mechanisms, MHY553 stimulated PPARα translocation into the nucleus and increased mRNA levels of its downstream genes related to fatty acid oxidation, including CPT-1A and ACOX1, without apparent change in lipogenesis signaling. Furthermore, MHY553 significantly suppresses inflammatory mRNA expression in old rats. In conclusion, MHY553 is a novel PPARα agonist that improved aged-induced hepatic steatosis, in part by increasing β-oxidation signaling and decreasing inflammation in the liver. MHY553 is a potential pharmaceutical agent for treating hepatic steatosis in aging.
In the present work, the corrosion properties of Mg-xSn-5Al-1Zn (x ¼ 0, 1, 5 and 9 mass%) alloys have been investigated. Potentiodynamic polarization and immersion tests were carried out in 3.5% NaCl solution of pH 7.2 at room temperature to measure the corrosion properties of Mg-xSn-5Al-1Zn (x ¼ 0, 1, 5, and 9 mass%) alloys. Microstrucral analysis shows the Mg 17 Al 12 and Mg 2 Sn phase were mainly precipitated along grain boundaries. With increase of the Sn contents, the volume fraction of the secondary phases, i.e. Mg 17 Al 12 and Mg 2 Sn phase, was increased. The corrosion resistance of Mg-xSn-5Al-1Zn alloys was improved by the Sn addition. Especially, the AZ51-5 mass%Sn alloy characterized the superior corrosion resistance in the studied alloys. It seems that the presence of Sn stabilized the Mg(OH) 2 layers on the surface of Mg alloys and the secondary phases effectively formed semi-continuous structures, resulting in a drastic improvement of corrosion resistance of the Mg alloys.
Nonalcoholic fatty liver disease (NAFLD) is frequently observed in obese and aged individuals. Peroxisome proliferator-activated receptors (PPARs) play a role in regulating hepatic lipid accumulation, a hallmark of NAFLD development. A PPAR pan agonist, 2-(4-(5,6-methylenedioxybenzo[d]thiazol-2-yl)-2-methylphenoxy)-2-methylpropanoic acid (MHY2013) has been shown to prevent fatty liver formation and insulin resistance in obese mice (db/db) model. However, the beneficial effects of MHY2013 in aged model remain unknown. In this study, we investigated whether MHY2013 alleviates hepatic lipid accumulation in aged Sprague-Dawley (SD) rats. We confirmed that MHY2013 increased the activities of three PPAR subtypes in HepG2 cells using luciferase assay. When administered orally in aged SD rats, MHY2013 markedly decreased the hepatic triglyceride levels without changes in body weight. Regarding underlying mechanisms, MHY2013 increased the mRNA levels of lipid oxidation-related genes, including carnitine palmitoyltransferase 1 (CPT1) and peroxisomal acyl-CoA oxidase 1 (ACOX1), without apparent change in the mRNA expression of lipogenesis-related genes. Furthermore, MHY2013 significantly increased systemic fibroblast growth factor 21 (FGF21) and adiponectin levels and suppressed inflammatory mRNA expression in the liver. In conclusion, MHY2013 alleviated age-related hepatic lipid accumulation, in part by upregulating β-oxidation signaling and suppressing inflammation in the liver. Therefore, MHY2013 is a potential pharmaceutical agent for treating age-related hepatic lipid accumulation.Key words aging; nonalcoholic fatty liver disease; MHY2013; peroxisome proliferator-activated receptor (PPAR) pan agonist; lipid oxidation Aging of vast majority of population is very recent phenomenon that has emerged as a direct consequence of the extension of lifespan. The aging process cause hepatic functional and structural impairments leading to metabolic risks.
The effects of Yb addition on the microstructure and mechanical properties of Mg-5Al alloy are investigated. The results indicate that the addition of Yb to the Mg-5Al alloy facilitates the formation of a thermally stable Al 2 Yb phase, the refinement of the microstructure and the suppression of the volume fraction of Mg 17 Al 12 phase in Mg-5Al alloy. Yb addition has little effect on the mechanical properties of the experimental alloys tested at room temperature. At elevated temperatures, however, the ultimate tensile strength (UTS) is significantly increased by Yb addition and Mg-5Al-1Yb has the highest UTS value than other experimental alloys. On the other hand, the yield strength (YS) increases at all tested temperatures due to the grain refinement and dispersion strengthening of the secondary phase. Meanwhile, the elongation (") of the experimental alloys decreases at all tested temperatures. Tensile fractographic analysis indicates that cleavage fracture is the dominant mechanism of the Mg-5Al and Mg-5Al-xYb alloys at room temperature. At elevated temperatures, however, the fracture mechanism of experimental alloys mainly changes from cleavage to quasi-cleavage fracture.
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