Quantified Metabolomics and Lipidomics Profiles Reveal Serum Metabolic Alterations and Distinguished Metabolites of Seven Chronic Metabolic Diseases

The co-occurrence of multiple chronic metabolic diseases
is highly
prevalent, posing a huge health threat. Clarifying the metabolic associations
between them, as well as identifying metabolites which allow discrimination
between diseases, will provide new biological insights into their
co-occurrence. Herein, we utilized targeted serum metabolomics and
lipidomics covering over 700 metabolites to characterize metabolic
alterations and associations related to seven chronic metabolic diseases
(obesity, hypertension, hyperuricemia, hyperglycemia, hypercholesterolemia,
hypertriglyceridemia, fatty liver) from 1626 participants. We identified
454 metabolites were shared among at least two chronic metabolic diseases,
accounting for 73.3% of all 619 significant metabolite–disease
associations. We found amino acids, lactic acid, 2-hydroxybutyric
acid, triacylglycerols (TGs), and diacylglycerols (DGs) showed connectivity
across multiple chronic metabolic diseases. Many carnitines were specifically
associated with hyperuricemia. The hypercholesterolemia group showed
obvious lipid metabolism disorder. Using logistic regression models,
we further identified distinguished metabolites of seven chronic metabolic
diseases, which exhibited satisfactory area under curve (AUC) values
ranging from 0.848 to 1 in discovery and validation sets. Overall,
quantitative metabolome and lipidome data sets revealed widespread
and interconnected metabolic disorders among seven chronic metabolic
diseases. The distinguished metabolites are useful for diagnosing
chronic metabolic diseases and provide a reference value for further
clinical intervention and management based on metabolomics strategy.