Analytical and Bioanalytical Chemistry

, Volume 408, Issue 11, pp 2963–2973 | Cite as

Lipidomic profiling of tryptophan hydroxylase 2 knockout mice reveals novel lipid biomarkers associated with serotonin deficiency

  • Rui Weng
  • Sensen Shen
  • Casey Burton
  • Li Yang
  • Honggang Nie
  • Yonglu Tian
  • Yu BaiEmail author
  • Huwei Liu
Research Paper
Part of the following topical collections:
  1. Young Investigators in Analytical and Bioanalytical Science


Serotonin is an important neurotransmitter that regulates a wide range of physiological, neuropsychological, and behavioral processes. Consequently, serotonin deficiency is involved in a wide variety of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, schizophrenia, and depression. The pathophysiological mechanisms underlying serotonin deficiency, particularly from a lipidomics perspective, remain poorly understood. This study therefore aimed to identify novel lipid biomarkers associated with serotonin deficiency by lipidomic profiling of tryptophan hydroxylase 2 knockout (Tph2−/−) mice. Using a high-throughput normal-/reversed-phase two-dimensional liquid chromatography–quadrupole time-of-flight mass spectrometry (NP/RP 2D LC–QToF-MS) method, 59 lipid biomarkers encompassing glycerophospholipids (glycerophosphocholines, lysoglycerophosphocholines, glycerophosphoethanolamines, lysoglycerophosphoethanolamines glycerophosphoinositols, and lysoglycerophosphoinositols), sphingolipids (sphingomyelins, ceramides, galactosylceramides, glucosylceramides, and lactosylceramides) and free fatty acids were identified. Systemic oxidative stress in the Tph2−/− mice was significantly elevated, and a corresponding mechanism that relates the lipidomic findings has been proposed. In summary, this work provides preliminary findings that lipid metabolism is implicated in serotonin deficiency.


Serotonin deficiency Tryptophan hydroxylase 2 knockout (Tph2−/−) mice Lipidomics Lipid biomarkers Two-dimensional liquid chromatography–quadrupole time-of-flight mass spectrometry (2D LC–QToF-MS) 



We thank Prof. Yi Rao and Dr. Yan Liu for providing the Tph2−/− mice and Rabia Khan for help in revising the manuscript. This research was financially supported by the National Natural Science Foundation of China (No. 21322505 and 21175008) and the Ministry of Science and Technology of China (No. 2012YQ09019409 and 2013YQ510391). Casey Burton received funding through a National Science Foundation Graduate Research Fellowship (#DGE-1011744).

Compliance with ethical standards

Vertebrate animal studies were approved by the Institutional Review Board of the Institutional Animal Care and Use Committee of Peking University. All experiments were carried out in accordance with the approved guidelines and conducted at the Laboratory Animal Center of Peking University which is a AAA-certified animal facility.

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

216_2015_9256_MOESM1_ESM.pdf (8 kb)
ESM 1 (PDF 7 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Rui Weng
    • 1
    • 2
  • Sensen Shen
    • 1
  • Casey Burton
    • 3
  • Li Yang
    • 1
  • Honggang Nie
    • 4
  • Yonglu Tian
    • 5
  • Yu Bai
    • 1
    Email author
  • Huwei Liu
    • 1
  1. 1.Beijing National Laboratory for Molecular Sciences, the Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular EngineeringPeking UniversityBeijingChina
  2. 2.Institute of Quality Standards and Testing Technology for Agro-ProductsChinese Academy of Agriculture SciencesBeijingChina
  3. 3.Department of Chemistry and Center for Single Cell, Single Nanoparticle, and Single Molecule MonitoringMissouri University of Science and TechnologyRollaUSA
  4. 4.Analytical Instrumentation CenterPeking UniversityBeijingChina
  5. 5.Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijingChina

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