Determination of a phospholipid signature for human Metabolic Syndrome using mass spectrometry-based metabolomic approaches

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Kozlowski_Rachel_MSc_2011.pdf (5.77 MB)

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2011-10-18

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Kozlowski, Rachel

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Abstract

Metabolic Syndrome (MetS) is an obesity-related disorder that predisposes an individual to several life-threatening diseases such as cardiovascular disease, hypertension and type 2 diabetes mellitus. The diagnosis of metabolic syndrome is based on the presence of at least 3 of the following 5 risk factors: elevated triglycerides, high blood pressure, high blood glucose, low HDL cholesterol and central adiposity. However, the biochemical mechanisms underlying the contribution of these irregularities are not fully understood. Currently, there is a need to better characterize MetS. Irregularity of lipid abundances, dyslipidemia, is known to be associated with MetS. However, little is known about the link between plasma phospholipids and human metabolic syndrome. In this study, mass spectrometry-based metabolomic approaches were employed using ultrahigh-resolution FTICR mass spectrometry to qualitatively analyze human plasma phospholipids and high-resolution QTOF mass spectrometry to quantitatively detect differences in the human plasma phospholipid profiles from 10 clinically-diagnosed metabolic syndrome patients and 8 lean healthy controls. The results point to the existence of a phospholipid signature of MetS. Five of the top twenty phospholipids contributing most to the difference in phospholipid abundance between the MetS and control group were identified using accurate mass-based database searching and MS/MS for structural confirmation. Relative differences in phospholipid abundances between MetS and controls for all top 20 phospholipids were shown to be statistically significant. These results may aid biomarker discovery and the accurate evaluation and prevention of diseases associated with dyslipidemia including human metabolic syndrome.

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obesity, plasma phospholipids, MetS

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http://hdl.handle.net/1828/3614

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