Profiling of Metabolome in the Plasma Following a circH19 Knockdown Intervention in Diet-Induced Obese Mice
Hanxin Zhao1, Dike Shi2, Weiwei Gui1
1Department of Endocrinology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
Abstract:
The circular RNA circH19 has been implicated in the regulation of gene expression and various biological processes, including obesity. Objectives: This study aimed to elucidate the metabolic changes in plasma after circH19 knockdown in a diet-induced obese (DIO) mouse model. Methods: Plasma samples were collected following the intervention and subjected to non-targeted metabolomics analysis using liquid chromatography-mass spectrometry (LC-MS). Metabolic profiling was performed to identify and quantify metabolites, followed by multivariate statistical analysis to discern differential metabolic signatures. Results: A total of 1250 features were quantified, resulting in the upregulation of 564 metabolites and the downregulation of 686 metabolites in the circH19 knockdown group compared to the control mice. Metabolic pathway analysis revealed disruptions in lipid metabolism, amino acid turnover, and energy production pathways. Notably, the intervention led to a substantial decrease in circulating lipids and alterations in the plasma amino acid profile, indicative of an impact on protein catabolism and anabolic processes. The observed shifts in lipid and amino acid metabolism suggest potential therapeutic avenues for obesity and related metabolic disorders. Conclusions: The circH19 knockdown in DIO mice led to significant alterations in plasma metabolites, highlighting its potential role in the regulation of obesity and metabolic disorders.
Insights
Knocking down circH19 in diet-induced obese mice significantly altered plasma metabolites, impacting lipid and amino acid pathways. This suggests circH19
Area of Science:
- Metabolomics
- Molecular Biology
- Obesity Research
Background:
- Circular RNA circH19 is involved in gene regulation and biological processes, including obesity.
- Diet-induced obesity (DIO) is a common model for studying metabolic disorders.
Purpose of the Study:
- To investigate the plasma metabolic profile changes following circH19 knockdown in DIO mice.
- To identify specific metabolic pathways affected by circH19 modulation in obesity.
Main Methods:
- Non-targeted metabolomics using liquid chromatography-mass spectrometry (LC-MS) on plasma samples.
- Multivariate statistical analysis to identify differential metabolic signatures.
- Metabolic pathway analysis to understand functional impacts.
Main Results:
- Quantification of 1250 metabolic features, with 564 upregulated and 686 downregulated metabolites post-circH19 knockdown.
- Significant disruptions observed in lipid metabolism, amino acid turnover, and energy production pathways.
- Substantial decrease in circulating lipids and altered plasma amino acid profiles.
Conclusions:
- circH19 knockdown induces significant plasma metabolic alterations in DIO mice.
- These metabolic shifts highlight circH19's role in regulating obesity and associated metabolic disorders.
- Findings suggest potential therapeutic targets for obesity and metabolic diseases.
