Metabolic alterations in healthy human adults associated with chronotypes-a pilot clinical trial

Abstract

Chronobiology pertains to the examination of biological rhythms. The phenotypic manifestation of the internal clock is referred to as chronotype. Currently, there exists a limited number of studies linking biomolecules and pathways to specific chronotypes. Metabolites, possess great versatility, and are crucial in defining the phenotype of an organism. Therefore, it would be of clinical significance to establish an association between the metabolite signature and chronotype. In our investigation, we conducted an analysis of the chronotypes of eight healthy volunteers using a validated ICER chronotype questionnaire, which is an adapted version of the Munich Chronotype Questionnaire (MCTQ). By employing rapid resolution liquid chromatography - tandem mass spectrometry (RRLC-MS) on serum samples from these volunteers, a comprehensive and unbiased profiling of metabolites was conducted to evaluate the signature metabolites and molecular pathways. Interestingly, the metabolic pathways of Purine, Glycerophospholipid, and Thiamine were noticed to be particularly prominent. Remarkable marker metabolites associated with morning and intermediate chronotypes included Thiamine triphosphate, Deoxyuridine, Cyclic GMP, Epinephrine, Glycocholic Acid, Adenosine triphosphate, Phosphoadenosine phosphosulfate, lysophospholipid, phosphatidylethanolamines, and phosphatidic acid. When analyzed in the intermediate and morning group, Adenosine triphosphate and glycoholic acid were found to be downregulated, while Phosphoadenosine phosphosulfate was upregulated. Our omics analysis clearly demonstrated a distinct differentiation between chronotypes based on their metabolism and associated pathways. Consequently, this offers a potential tool for the identification and characterization of marker compounds to assign chronotypes, thereby facilitating the incorporation of chronotherapy in disease diagnosis.