Metabolic Fingerprints of Circulating IGF-1 and the IGF-1/IGFBP-3 Ratio: A Multifluid Metabolomics Study

• Published in: The journal of clinical endocrinology and metabolism Vol. 101; no. 12; pp. 4730 - 4742
• Main Authors: Knacke, Henrike, Pietzner, Maik, Do, Kieu Trinh, Römisch-Margl, Werner, Kastenmüller, Gabi, Völker, Uwe, Völzke, Henry, Krumsiek, Jan, Artati, Anna, Wallaschofski, Henri, Nauck, Matthias, Suhre, Karsten, Adamski, Jerzy, Friedrich, Nele
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.12.2016; Copyright by The Endocrine Society
• Subjects: Adult; Aged; Amino acids; Bradykinin; Cardiovascular disease; Cardiovascular diseases; Cortisol; Diabetes mellitus; Female; Germany - epidemiology; Hormones; Humans; Insulin-Like Growth Factor Binding Protein 3 - metabolism; Insulin-like growth factor I; Insulin-Like Growth Factor I - metabolism; Insulin-like growth factor-binding protein 3; Insulin-like growth factors; Intermediates; Male; Mass spectroscopy; Metabolic syndrome; Metabolites; Metabolome - physiology; Metabolomics; Metabolomics - methods; Middle Aged; Molecular modelling; Phospholipids; Registries; Sex differences; Sex Factors; Steroid hormones; Therapeutic targets; Young Adult
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2016-2588

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, and diabetes, or have previously been found to associate with differentiation 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, we showed an association between IGF-1 and pipecolate, a metabolite 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 syndrome-associated biomarkers and therapeutic targets.