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. / Graduate

The ability to extrapolate nutritional intervention data from experimental rodent models to humans requires standardization of dietary design. The inability to translate the level of nutrients from animal models to humans has contributed to contradictory findings between species. It is hypothesized that dietary linoleic acid (LA) promotes chronic and acute diseases by enriching tissues with arachidonic acid (AA), its downstream metabolite. However, levels of LA in rodent diets are notoriously erratic making interspecies comparisons unreliable. Therefore, the ability to extrapolate the biological effects of dietary LA from experimental rodents to humans necessitates an allometric scaling model that is rooted within a human equivalent context. To determine the physiological effect of dietary LA on tissue AA, a mathematical model for extrapolating nutrients based on energy was designed to mimic human equivalent doses. C57BL/6J mice were divided into 9 groups fed a background diet equivalent to that of the US diet (including LA, ALA, AA, EPA, DHA) with supplemental doses of LA (up to 2.3x) or AA (up to 5x). Changes in the phospholipid fatty acid compositions were monitored in plasma and erythrocytes and compared to data from humans supplemented with equivalent doses of LA or AA. Increasing dietary LA had little effect on tissue AA, while supplementing diets with AA significantly increased tissue AA levels, recapitulating results from human trials. Thus, interspecies comparisons for dietary LA between rodents and humans can be achieved when rodents are provided human equivalent doses based on differences in metabolic activity as defined by energy consumption.