Potential Mechanism of Chinese herbal formula Sijunzi Decoction in Treating Gastric Cancer
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ABSTRACT:
INSTRUMENT(S): DNBSEQ-T7, SPF Animal Room, Animal Experiment Facility, Centrifuge, Nucleic Acid Quantification Instrument, Dr. Tom Multi-omics Data Mining System, Biosafety Cabinet, Liquid Nitrogen Tank, -80°C Freezer, PCR Thermocycler, Fragment Analyzer
ORGANISM(S): Mus musculus
SUBMITTER: Xiaoyu Luo
PROVIDER: E-MTAB-15788 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Fibroblast growth factor 21 (Fgf21) has emerged as a potential plasma marker to diagnose non-alcoholic fatty liver disease (NAFLD). To study the molecular processes underlying the association of plasma Fgf21 with NAFLD, we explored the liver transcriptome data of a mild NAFLD model of aging C57BL/6J mice at 12, 24, and 28 months of age. The plasma Fgf21 level significantly correlated with intrahepatic triglyceride content. At the molecular level, elevated plasma Fgf21 levels were associated with dysregulated metabolic and cancer-related pathways. The up-regulated Fgf21 levels in NAFLD were implied to be a protective response against the NAFLD-induced adverse effects, e.g. lipotoxicity, oxidative stress and endoplasmic reticulum stress. An in vivo PPARalpha challenge demonstrated the dysregulation of PPARalpha signalling in the presence of NAFLD, which resulted in a stochastically increasing hepatic expression of Fgf21. Notably, elevated plasma Fgf21 was associated with declining expression of Klb, Fgf21â??s crucial co-receptor, which suggests a resistance to Fgf21. Therefore, although liver fat accumulation is a benign stage of NAFLD, the elevated plasma Fgf21 likely indicated vulnerability to metabolic stressors that may contribute towards progression to end-stage NAFLD. In conclusion, plasma levels of Fgf21 reflect liver fat accumulation and dysregulation of metabolic pathways in the liver. Male C57Bl/6J mice were divided to 3 dietary intervention groups: Control (AIN-93W), 30% calorie restriction (CR; AIN-93W-CR) and medium fat (MF; AIN-93W-MF; 25% energy from fat). Dietary interventions started at the age of 9 weeks and sacrifice was performed at the age of 6, 12, 24 and 28 months. We performed various measurements on metabolic parameters and gene expression analysis. This entry represents the microarray data.
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Project description:SCOPE: We investigated whether a novel dietary intervention consisting of an every-other-week calorie-restricted diet could prevent nonalcoholic fatty liver disease (NAFLD) development induced by a medium-fat (MF) diet. METHODS AND RESULTS: Nine-week-old male C57BL/6J mice received either a (i) control (C), (ii) 30E% calorie restricted (CR), (iii) MF (25E% fat), or (iv) intermittent (INT) diet, a diet alternating weekly between 40E% CR and an ad libitum MF diet until sacrifice at the age of 12 months. The metabolic, morphological, and molecular features of NAFLD were examined. The INT diet resulted in healthy metabolic and morphological features as displayed by the continuous CR diet: glucose tolerant, low hepatic triglyceride content, low plasma alanine aminotransferase. In contrast, the C- and MF-exposed mice with high body weight developed signs of NAFLD. However, the gene expression profiles of INT-exposed mice differed to those of CR-exposed mice and showed to be more similar with those of C- and MF-exposed mice with a comparable body weight. CONCLUSIONS: Our study reveals that the INT diet maintains metabolic health and reverses the adverse effects of the MF diet, thus effectively prevents the development of NAFLD in 12-month-old male C57BL/6J mice. Male C57Bl/6J mice were divided to 4 dietary intervention groups: Control (AIN-93W), 30% calorie restriction (CR; AIN-93W-CR), medium fat (MF; AIN-93W-MF; 25% energy from fat) and intermittent diet (INT; weekly alternating diet between AIN-93W-MF ad lib and 40% CR of AIN-93W). We performed various measurements on metabolic parameters and gene expression analysis on the liver. This entry represents the microarray data of the liver gene expression of each mouse.
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