期刊
CELL METABOLISM
卷 21, 期 6, 页码 898-904出版社
CELL PRESS
DOI: 10.1016/j.cmet.2015.05.004
关键词
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资金
- NIH [R01DK067158]
- Robert A. Welch Foundation [I-1558, I-1275]
- Cancer Prevention and Research Institute of Texas [R1121, RP120613]
- Swiss National Foundation Early Postdoc Mobility Fellowship
- Howard Hughes Medical Institute
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.
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