Detection of FGF15 in plasma by stable isotope standards and capture by anti-peptide antibodies and targeted mass spectrometry

Takeshi Katafuchi, Daria Esterházy, Andrew Lemoff, Xunshan Ding, Varun Sondhi, Steven A. Kliewer, Hamid Mirzaei, David J. Mangelsdorf

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

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, β-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.

Original languageEnglish (US)
Pages (from-to)898-904
Number of pages7
JournalCell Metabolism
Volume21
Issue number6
DOIs
StatePublished - Jun 2 2015

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

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