Proteomic Analysis of Human Plasma during Intermittent Fasting
Harney DJ, Hutchison AT, Hatchwell L, Humphrey SJ, James DE, Hocking S, Heilbronn LK, Larance M
Journal of proteome research · 99 citations
How it was studied
- Design
- Randomized controlled trial (indexed by PubMed)
- Studied in
- People
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- University or hospital
- Cancer Institute NSW
- Government
- Australian Research Council
- Government
- National Health and Medical Research Council
- Grants
- Australian Research Council (FT120100027); Cancer Institute NSW (15/FRL/1-06A); National Health and Medical Research Council (1023401); National Health and Medical Research Council (1120475)
Based on 3 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2019-03-20 · J Proteome Res · vol. 18 · issue 5 · pp. 2228–2240
- Publisher
- American Chemical Society
- Cited
- 116 citations · more than 96% of similar papers · 5.1× the field average
- Impact
- Top 10% most cited in its field
- References
- 72 works
- Access
- Open access (hybrid journal) · OTHER-OA
- Research areas
- Dietary Effects on Health · Adipose Tissue and Metabolism · Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- Human plasma, Chemistry, Computational biology, Biology, Chromatography
- MeSH
- humans, triglycerides, lipoproteins, hdl, apolipoproteins a, specimen handling, chromatography, liquid, fasting, longitudinal studies, proteomics, gene expression, particle size, databases, protein, adult, aged, middle aged, female, lipid metabolism, apolipoprotein c-ii, apolipoprotein c-iii, tandem mass spectrometry, solid phase extraction, printing, three-dimensional
8 authors
From AU
- Dylan HarneyThe University of Sydney
- Amy T. HutchisonThe University of Adelaide
- Luke HatchwellThe University of Sydney
- Sean J. HumphreyThe University of Sydney
- David Ernest JamesThe University of Sydney
- SAMANTHA L. HOCKINGThe University of Sydney
Abstract
Intermittent fasting (IF) increases lifespan and decreases metabolic disease phenotypes and cancer risk in model organisms, but the health benefits of IF in humans are less clear. Human plasma derived from clinical trials is one of the most difficult sample sets to analyze using mass spectrometry-based proteomics due to the extensive sample preparation required and the need to process many samples to achieve statistical significance. Here, we describe an optimized and accessible device (Spin96) to accommodate up to 96 StageTips, a widely used sample preparation medium enabling efficient and consistent processing of samples prior to LC-MS/MS. We have applied this device to the analysis of human plasma from a clinical trial of IF. In this longitudinal study employing 8-weeks IF, we identified significant abundance differences induced by the IF intervention, including increased apolipoprotein A4 (APOA4) and decreased apolipoprotein C2 (APOC2) and C3 (APOC3). These changes correlated with a significant decrease in plasma triglycerides after the IF intervention. Given that these proteins have a role in regulating apolipoprotein particle metabolism, we propose that IF had a positive effect on lipid metabolism through modulation of HDL particle size and function. In addition, we applied a novel human protein variant database to detect common protein variants across the participants. We show that consistent detection of clinically relevant peptides derived from both alleles of many proteins is possible, including some that are associated with human metabolic phenotypes. Together, these findings illustrate the power of accessible workflows for proteomics analysis of clinical samples to yield significant biological insight.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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