First Author | Katafuchi T | Year | 2015 |
Journal | Cell Metab | Volume | 21 |
Issue | 6 | Pages | 898-904 |
PubMed ID | 26039452 | Mgi Jnum | J:226123 |
Mgi Id | MGI:5695813 | Doi | 10.1016/j.cmet.2015.05.004 |
Citation | Katafuchi T, et al. (2015) Detection of FGF15 in plasma by stable isotope standards and capture by anti-peptide antibodies and targeted mass spectrometry. Cell Metab 21(6):898-904 |
abstractText | Fibroblast growth factor 15 (FGF15) has been proposed as a postprandial hormone that signals from intestine to liver to regulate bile acid and carbohydrate homeostasis. However, detecting FGF15 in blood using conventional techniques has proven difficult. Here, we describe a stable isotope standards and capture by anti-peptide antibodies (SISCAPA) assay that combines immuno-enrichment with selected reaction monitoring (SRM) mass spectrometry to overcome this issue. Using this assay, we show that FGF15 circulates in plasma in an FXR and circadian rhythm-dependent manner at concentrations that activate its receptor. Consistent with the proposed endocrine role for FGF15 in liver, mice lacking hepatocyte expression of the obligate FGF15 co-receptor, beta-Klotho, have increased bile acid synthesis and reduced glycogen storage despite having supraphysiological plasma FGF15 concentrations. Collectively, these data demonstrate that FGF15 functions as a hormone and highlight the utility of SISCAPA-SRM as a sensitive assay for detecting low-abundance proteins in plasma. |