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Assessing Whole-Body Lipid-Handling Capacity in Mice
Published on: November 24, 2020
Multi-Omics Identified THDCA as a Key Contributor to Hyperlipidemia and as a Potential Therapeutic Agent
Zhaohuan Lou1, Liping Han1, Yuanguo Qu2
1School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, 310053 Hangzhou, Zhejiang, China.
Insights
Taurohyodeoxycholic acid (THDCA) shows promise for treating hyperlipidemia, a condition linked to cardiovascular disease. This study identified THDCA as a potential lipid-lowering compound and biomarker for hyperlipidemia.
Area of Science:
- Metabolomics
- Microbiome Research
- Cardiovascular Disease Research
Background:
- Hyperlipidemia (HLP) is a growing concern linked to cardiovascular diseases due to changing dietary habits.
- Developing novel treatments for hyperlipidemia is crucial given its increasing incidence and mortality.
- This study explores endogenous bile acid compounds as potential therapeutic agents for HLP.
Purpose of the Study:
- To identify novel therapeutic compounds for hyperlipidemia through multi-omics analysis.
- To investigate the role of bile acids in hyperlipidemia.
- To evaluate the lipid-lowering potential of taurohyodeoxycholic acid (THDCA).
Main Methods:
- Established hyperlipidemia models in rats and mice using high-fat diets.
- Conducted integrated analysis of lipid metabolism, 16S rRNA intestinal flora, and targeted bile acid sequencing.
- Verified the anti-hyperlipidemia effects of THDCA in a mouse model.
Main Results:
- Significant alterations in bile acid synthesis pathways were observed in hyperlipidemia models.
- High-fat diet impacted primary and secondary bile acid biosynthesis, as shown by 16S rRNA sequencing.
- Taurohyodeoxycholic acid (THDCA) was identified as a potential biomarker and lipid-lowering compound, with verified efficacy in mice.
Conclusions:
- Taurohyodeoxycholic acid (THDCA) is identified as a potential biomarker for hyperlipidemia.
- THDCA demonstrates significant potential for the treatment of hyperlipidemia.
- This research highlights the therapeutic potential of THDCA in managing lipid levels.
Background:
In recent years, with the change in human dietary habits, hyperlipidemia (HLP) has become a common chronic disease. Hyperlipidemia is closely related to the incidence of cardiovascular diseases. Due to the increasing incidence and mortality from cardiovascular diseases, it is imperative to develop new medications for reducing lipid levels. With the aim of discovering new treatment options for hyperlipidemia, we conducted a multi-omics analysis of a potential endogenous bile acid compound.
Methods:
Two hyperlipidemia models were established by feeding rats and mice with a high-fat diet. Serum and fecal specimens of rats with hyperlipidemia were collected. Through the combined analysis of lipid metabolism sequencing, 16S RNA intestinal flora sequencing, and bile acid targeted metabolism sequencing, taurohyodeoxycholic acid (THDCA) was found to be a potential lipid-lowering compound. A mouse hyperlipidemia model was developed to verify the anti-hyperlipidemia function of THDCA.
Results:
Analysis of serum lipid metabolites revealed that the synthesis of bile acid was one of the metabolic pathways that showed significant alterations. 16S RNA sequencing of intestinal flora also found that high-fat diet intake greatly influenced both primary and secondary bile acid biosynthesis. Analysis of bile acid metabolites in the serum and liver tissue found that THDCA in the secondary bile acids is a potential biomarker of hyperlipidemia. Verification experiments in mice confirmed the beneficial function of THDCA in lowering abnormal lipid levels induced by a high-fat diet.
Conclusions:
THDCA has been identified as a biomarker of hyperlipidemia and has shown potential for the treatment of hyperlipidemia.
