Metabolic fingerprints of circulating IGF-1 and the IGF-1/IGFBP-3 Ratio: A multifluid metabolomics study

Henrike Knacke, Maik Pietzner, Kieu Trinh Do, Werner Römisch-Margl, Gabi Kastenmüller, Uwe Völker, Henry Völzke, Jan Krumsiek, Anna Artati, Henri Wallaschofski, Matthias Nauck, Karsten Suhre, Jerzy Adamski, Nele Friedrich

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13 Citations (Scopus)

Abstract

Objective: IGF-1 is known for its various physiological and severe pathophysiological effects on human metabolism; however, underlying molecular mechanisms still remain unsolved. To reveal possible molecular mechanisms mediating these effects, for the first time, we associated serum IGF-1 levels with multifluid untargeted metabolomics data. Methods: Plasma/urine samples of 995 nondiabetic participants of the Study of Health in Pomerania were characterized by mass spectrometry. Sex-specific linear regression analyses were performed to assess the association of IGF-1 and IGF-1/IGF binding protein 3 ratio with metabolites. Additionally, the predictive ability of the plasma and urine metabolome for IGF-1 was assessed by orthogonal partial least squares analyses. Results and Conclusions: We revealed a multifaceted image of associated metabolites with large sex differences. Confirming previous reports, we detected relations between IGF-1 and steroid hormones or related intermediates. Furthermore, various associated metabolites were previously mentioned regarding IGF-1-associated diseases, eg, betaine and cortisol in cardiovascular disease and metabolic syndrome,lipid disorders,anddiabetes,orhavepreviouslybeenfoundtoassociatewithdifferentiation and proliferation or mitochondrial functionality, eg, phospholipids. bradykinin, fatty acid derivatives, and cortisol, which were inversely associated with IGF-1, might establish a link of IGF-1 with inflammation. For the first time,weshowedanassociationbetweenIGF-1andpipecolate,ametabolite linked to amino acid metabolism. Our study demonstrates that IGF-1 action on metabolism is tractable, even in healthy subjects, and that the findings provide a solid basis for further experimental/clinical investigation, eg, searching for inflammatory or cardiovascular disease- or metabolic syndromeassociated biomarkers and therapeutic targets.

Original languageEnglish
Pages (from-to)4730-4742
Number of pages13
JournalJournal of Clinical Endocrinology and Metabolism
Volume101
Issue number12
DOIs
Publication statusPublished - 1 Dec 2016
Externally publishedYes

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Knacke, H., Pietzner, M., Do, K. T., Römisch-Margl, W., Kastenmüller, G., Völker, U., Völzke, H., Krumsiek, J., Artati, A., Wallaschofski, H., Nauck, M., Suhre, K., Adamski, J., & Friedrich, N. (2016). Metabolic fingerprints of circulating IGF-1 and the IGF-1/IGFBP-3 Ratio: A multifluid metabolomics study. Journal of Clinical Endocrinology and Metabolism, 101(12), 4730-4742. https://doi.org/10.1210/jc.2016-2588