Ursolic acid attenuates hepatic steatosis, fibrosis, and insulin resistance by modulating the circadian rhythm pathway in diet-induced obese mice
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PROVIDER: PRJNA492286 | ENA |
REPOSITORIES: ENA
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Project description:Background/Objectives: The aim of the current study was to elucidate the effects of long-term supplementation with dietary ursolic acid (UR) on obesity and associated comorbidities, such as hepatic fibrosis, by analyzing transcriptional and metabolic responses, focusing on the role of UR in the modulation of the circadian rhythm pathway in particular. Subjects/Methods: C57BL/6J mice were divided into three groups and fed a normal diet, high-fat diet (HFD), or high-fat + 0.05% (w/w) UR diet for 16 weeks. Results: Oligonucleotide microarray profiling revealed that the liver transcriptome was more significantly altered by UR supplementation than that of the skeletal muscle and epididymal white adipose tissue, suggesting that UR is an effective regulator of the liver transcriptome. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway mapper analyses showed that canonical pathways associated with the “circadian rhythm” and “extracellular matrix (ECM)-receptor interactions” were effectively regulated by UR in the liver. UR altered the expression of various clock and clock-controlled genes (CCGs), which may be linked to the improvement of hepatic steatosis and fibrosis via lipid metabolism control and detoxification enhancement. UR reduced excessive reactive oxygen species production via an increase in plasma paraoxonase activity, adipokine/cytokine dysregulation, and ECM accumulation in the liver, which also contributed to improve hepatic lipotoxicity and fibrosis. In addition, UR treatment improved and normalized pancreatic islet dysfunction, and suppressed hepatic gluconeogenesis, thereby reducing obesity-associated insulin resistance in HFD-fed mice. Conclusions: Therapeutic approaches targeting hepatic circadian clock and CCGs using UR may ameliorate the deleterious effects of diet-induced obesity and associated complications such as hepatic fibrosis.
2018-09-21 | GSE120243 | GEO
Project description:The aim of the current study was to elucidate the effects of long-term supplementation with dietary ursolic acid (UR) on obesity and associated comorbidities by analyzing transcriptional and metabolic responses, focusing on the role of UR in the modulation of the circadian rhythm pathway in particular. C57BL/6J mice were divided into three groups and fed a normal diet, high-fat diet, or high-fat + 0.05% (w/w) UR diet for 16 weeks. Oligonucleotide microarray profiling revealed that UR is an effective regulator of the liver transcriptome, and canonical pathways associated with the "circadian rhythm" and "extracellular matrix (ECM)⁻receptor interactions" were effectively regulated by UR in the liver. UR altered the expression of various clock and clock-controlled genes (CCGs), which may be linked to the improvement of hepatic steatosis and fibrosis via lipid metabolism control and detoxification enhancement. UR reduced excessive reactive oxygen species production, adipokine/cytokine dysregulation, and ECM accumulation in the liver, which also contributed to improve hepatic lipotoxicity and fibrosis. Moreover, UR improved pancreatic islet dysfunction, and suppressed hepatic gluconeogenesis, thereby reducing obesity-associated insulin resistance. Therapeutic approaches targeting hepatic circadian clock and CCGs using UR may ameliorate the deleterious effects of diet-induced obesity and associated complications such as hepatic fibrosis.
| S-EPMC6266464 | biostudies-literature
Project description:This investigation scrutinizes the implications and mechanistic underpinnings of ursolic acid's effect on busulfan-induced oligospermia in mouse models. A single intraperitoneal injection at a dose of 30mg/kg of busulfan induced oligospermia, and two weeks later, the mice were treated with varied dosages of ursolic acid (10, 30, and 50 mg/kg w.t., respectively) daily for four consecutive weeks. Following this, a meticulous analysis of epididymal sperm parameters encompassing concentration and motility were undertaken using a computer-assisted sperm analysis system. The histopathology of the mice testes was performed utilizing hematoxylin and eosin staining, and the cytoskeleton regeneration of the testicular tissues was analyzed via immunofluorescent staining. Serum hormone levels (including testosterone, luteinizing hormone, and follicle-stimulating hormone) and reactive oxygen species levels (inclusive of reactive oxygen species and malondialdehyde) were gauged employing corresponding specific enzyme-linked immunosorbent assay kits. Differentially expressed genes of testicular mRNA between oligospermia and ursolic acid treatments were identified by RNA sequencing analysis. The results revealed that a dosage of 50 mg/kg ursolic acid treatment could increase the concentration of epididymal sperm in oligospermia mice, promote the recovery of testicular morphology, regulate hormone levels and ameliorate oxidative damage. The mechanism research results indicated that ursolic acid increased the expression level of genes related to motor proteins in oligospermia mice.
2024-02-17 | GSE251662 | GEO
Project description:Ursolic acid attenuates oligospermia in busulfan-induced mice by promoting motor proteins
| PRJNA1055032 | ENA
Project description:For additional details see Ebert et al, Identification and Small Molecule Inhibition of an ATF4-dependent Pathway to Age-related Skeletal Muscle Weakness and Atrophy. Weight-matched cohorts of 22-month-old male C57BL/6 mice were provided ad libitum access to standard chow (control) or standard chow supplemented with 0.27% ursolic acid (UA) or 0.05% tomatidine (TM) for 2 months. After the 2 month treatment period, quadriceps femoris muscles were harvested. mRNA levels in muscles harvested from ursolic acid or tomatidine fed mice were normalized to levels in muscles fed control diet.
2015-09-03 | E-GEOD-72651 | biostudies-arrayexpress
Project description:Hepatic steatosis is a very common response to liver injury and often attributed to metabolic disorders. Prior studies have demonstrated the efficacy of a biotechnologically produced oyster mushroom (Pleurotus sajor-caju, PSC) in alleviating hepatic steatosis in obese Zucker rats. This study aims to elucidate molecular events underlying the anti-steatotic effects of PSC.
2021-07-27 | PXD022905 | Pride
Project description:The goal of these studies was to determine the effects of ursolic acid on skeletal muscle mRNA levels in wild-type mice
2011-06-08 | GSE28017 | GEO
Project description:In this study, we repoort the protective effect of ursolic acid (UA) on vascular calcification in chronic kidney disease. To elucidate the molecular mechanism underlying the anti-vascular calcification effect of UA, we performed RNA-seq to identify the gene expresion under UA treatmment.
2024-09-13 | GSE276910 | GEO
Project description:Total RNA was isolated from 3 colonic tissues of each treatment group using the Qiagen RNeasy kit following the manufacturers' protocol. RNA samples with good quality control (RIN values>8) were sequenced using Hiseq-2500 by Novogene. Ursolic acid (UA), Dextran sulfate sodium (DSS)."Con" group stands for normal group, "DSS" group stands for DSS induced group, "UA_DSS" group stands for UA Preventive DSS induced group, "DSS_UA" group stands for UA Treatment DSS induced group.
2020-05-16 | GSE150688 | GEO
Project description:Nonalcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance. The peroxisome proliferator-activated receptor (PPAR) activators, thiazolidinediones, (TZDs), are insulin sensitizers used as a treatment for NAFLD. However, TZDs are a controversial treatment for NAFLD because of conflicting results regarding hepatic steatosis and fibrosis. To evaluate a possible effective drug for treatment of NAFLD, we investigated the effects of a newly developed TZD, lobeglitazone, with an emphasis on hepatic lipid metabolism. Lobeglitazone treatment for 4 weeks in high fat diet- (HFD-) induced obese mice (HL group) improved insulin resistance and glucose intolerance compared to HFD-induced obese mice (HU group). The gene levels related to hepatic gluconeogenesis also decreased after treatment by lobeglitazone. The livers of mice in the HL group showed histologically reduced lipid accumulation, with lowered total plasma cholesterol and triglyceride levels. In addition, the HL group significantly decreased the hepatic expression of genes associated with lipid synthesis, cholesterol biosynthesis, and lipid droplet development and increased the hepatic expression of genes associated with fatty acid β-oxidation, thus suggesting that lobeglitazone decreased hepatic steatosis and reversed hepatic lipid dysregulation. Livers with steatohepatitis contained increased levels of PPARγ and phosphorylated PPARγ at serine 273, leading to downregulation of expression of genes associated with insulin sensitivity. Notably, the treatment of lobeglitazone increased the protein levels of PPARα and diminished levels of PPARγ phosphorylated at serine 273, which were increased by a HFD, suggesting that induction of PPARα and posttranslational modification of PPARγ in livers by lobeglitazone might be an underlying mechanism of the improvement seen in NAFLD. Taken together, our data showed that lobeglitazone might be an effective treatment for NAFLD.
| S-EPMC6020545 | biostudies-literature