Revealing metabolic pathways relevant to prediabetes based on metabolomics profiling analysis

Area of Science:

• Metabolomics
• Biochemistry
• Physiology

Background:

• Dahl salt-sensitive (SS) rats exhibit prediabetes characteristics, including impaired glucose tolerance (IGT).
• Understanding metabolic shifts during prediabetes is crucial for preventing progression to diabetes.

Purpose of the Study:

• To investigate the impact of high glucose intake on prediabetes in SS rats.
• To identify metabolic pathways involved in the pathophysiology of prediabetes to diabetes transition.
• To compare these effects with salt-resistant SS.13BN rats.

Main Methods:

• SS rats and SS.13BN rats were fed normal chow with or without a 10% glucose solution for five weeks.
• Serum and liver tissue metabolites were analyzed using biochemical and metabolomics techniques.
• Multivariate, pathway enrichment, and metabolic correlation network analyses were performed.

Main Results:

• High glucose intake significantly increased serum triglyceride (TG) and decreased serum total cholesterol (TC) in SS rats.
• Metabolic pathway analysis indicated interference with galactose, glyoxylate, and dicarboxylate metabolism.
• Hepatic l-lactic acid increased in SS rats, while serum urea and l-valine showed higher metabolic centrality.

Conclusions:

• High glucose intake exacerbates hypertriglyceridemia and lowers serum TC in prediabetic rats.
• Galactose, glyoxylate, and dicarboxylate metabolism are significantly altered.
• l-lactic acid, l-valine, and urea are identified as potential biomarkers for diabetes progression.