Comprehensive Metabolic Profiling Reveals a Lipid-rich Fingerprint of Free Thyroxine Far Beyond Classical Parameters.

Comprehensive Metabolic Profiling Reveals a Lipid-rich Fingerprint of Free Thyroxine Far Beyond Classical Parameters.

J Clin Endocrinol Metab. 2018 Mar 12;:

Authors: Lange T, Budde K, Homuth G, Kastenmüller G, Artati A, Krumsiek J, Völzke H, Adamski J, Petersmann A, Völker U, Nauck M, Friedrich N, Pietzner M

Abstract
Objective: Thyroid hormones are ubiqiutiously involved in human metabolism. However, the precise molecular patterns associated with alterations in thyroid hormones levels remain to be explored in detail. A number of recent studies took great advantage of metabolomics profiling to outline metabolic actions of thyroid hormones in humans.
Methods: Among 952 participants of the Study of Health in Pomerania data on serum free thyroxine (FT4) and thyrotropin (TSH) as well as comprehensive (non-)targeted metabolomics data of plasma and urine samples were available. Linear regression analyses were performed to assess the association between FT4 or TSH and metabolite levels.
Results and Conclusion: After accounting for major confounders 106 out of 613 plasma metabolites were significantly associated with FT4. Associations in urine were minor (12 out of 587). The majority of the plasma metabolites consisted of lipid species and subsequent analysis of highly resolved lipoprotein subclasses measured by 1H-NMR spectroscopy revealed a consistent decrease in varoius of these species (e.g. phospholipids) and large LDL- as well as small HDL-particles. The latter was unique to men. Several polyunsaturated and saturated fatty acids displayed an association with FT4 in women only. A random forest-based variable selection approach using phenotypic characteristics revealed higher alcohol intake in men and an adverse thyroid state as well as the menopause in women as putative mediating factors. In general, our observations confirmed the lipolytic and lipogenic effect of thyroid hormones even in the physiological range and revealed different phenotypic characteristics, e.g. lifestyle differences, as possible confounders for sex-specific findings.

PMID: 29546278 [PubMed - as supplied by publisher]

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