Analysis of the Adult Human Plasma Metabolome

Lawton, Kay A.; Berger, Alvin; Mitchell, Matthew; Milgram, K. Eric; Evans, Anne M.; Guo, Lining; Hanson, Richard W.; Kalhan, Satish C.; Ryals, John; Milburn, Michael V.

doi:10.2217/14622416.9.4.383

Cited by 441 publications

(405 citation statements)

References 24 publications

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“…Given that sex differences in the metabolome and in aspirin response have been reported previously,1, 2, 23, 29 we first assessed whether the effect of aspirin on oxylipids was sex dependent. We compared oxylipid levels pre‐ and post aspirin in men versus women.…”

Section: Resultsmentioning

confidence: 99%

Oxylipid Profile of Low‐Dose Aspirin Exposure: A Pharmacometabolomics Study

Ellero‐Simatos¹,

Beitelshees

Lewis

et al. 2015

JAHA

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BackgroundWhile aspirin is a well‐established and generally effective anti‐platelet agent, considerable inter‐individual variation in drug response exists, for which mechanisms are not completely understood. Metabolomics allows for extensive measurement of small molecules in biological samples, enabling detailed mapping of pathways involved in drug response.Methods and ResultsWe used a mass‐spectrometry‐based metabolomics platform to investigate the changes in the serum oxylipid metabolome induced by an aspirin intervention (14 days, 81 mg/day) in healthy subjects (n=156). We observed a global decrease in serum oxylipids in response to aspirin (25 metabolites decreased out of 30 measured) regardless of sex. This decrease was concomitant with a significant decrease in serum linoleic acid levels (−19%, P=1.3×10−5), one of the main precursors for oxylipid synthesis. Interestingly, several linoleic acid‐derived oxylipids were not significantly associated with arachidonic‐induced ex vivo platelet aggregation, a widely accepted marker of aspirin response, but were significantly correlated with platelet reactivity in response to collagen.ConclusionsTogether, these results suggest that linoleic acid‐derived oxylipids may contribute to the non‐COX1 mediated variability in response to aspirin. Pharmacometabolomics allowed for more comprehensive interrogation of mechanisms of action of low dose aspirin and of variation in aspirin response.

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Section: Resultsmentioning

confidence: 99%

Oxylipid Profile of Low‐Dose Aspirin Exposure: A Pharmacometabolomics Study

Ellero‐Simatos¹,

Beitelshees

Lewis

et al. 2015

JAHA

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“…Certain prior studies have examined the influence of ethnicity on PFAA profiles. Lawton et al (2008) measured plasma metabolites in healthy Europeans, African‐Americans and Hispanics; their findings demonstrated that among these populations, ethnicity exerts only limited effects on concentrations of PFAAs. Another group measured PFAA concentrations in Greenlanders and Danes and reported that residence exerted the strongest influence on PFAA concentrations; ethnicity and diet had little to no effect on these concentrations, although ethnicity was weakly related to the plasma concentrations of Glu, His, Cit, and Arg (Pedersen et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Plasma amino acid profiles in healthy East Asian subpopulations living in Japan

Nakamura

Nishikata

Kawai

et al. 2015

American J Hum Biol

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ObjectivesProfiles of plasma free amino acids (PFAAs) have been utilized as biomarkers to detect various diseases. However, few studies have investigated whether ethnicity or specific subpopulations within East Asia influence PFAA concentrations.MethodsA total of 95 healthy volunteers living in Japan, including 31 Japanese individuals, 36 Korean individuals and 28 Chinese individuals, were enrolled. Participants’ PFAA levels were measured by high‐performance liquid chromatography mass spectrometry, and the effects of factors such as sex, age, body mass index (BMI) and subpopulation on PFAA profiles were analyzed.ResultsWith the exception of glutamine and α‐aminobutyric acid, there were no significant differences among the three examined subpopulations with respect to either the means or the distributions of PFAA concentrations. A multiple regression analysis revealed that most of the PFAA concentrations were significantly related to sex. Ornithine concentrations, glutamate concentrations, and glutamine and α‐aminobutyric acid concentrations were significantly associated with age, BMI, and Chinese subpopulation, respectively.ConclusionThe study results indicate that the contributions of subpopulation within East Asia to PFAA profiles are small, particularly relative to the contributions provided by sex. Am. J. Hum. Biol. 28:236–239, 2016. © 2015 The Authors American Journal of Human Biology Published by Wiley Periodicals, Inc.

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“…These data suggest a two-switch model for the circannual rhythm of hibernation whereby the torporarousal cycle is temporally segregated from the summer-winter cycle such that torpor-arousal occurs only in winter (36). However, because of limitations of previous studies in either the number of metabolites or the number of physiological stages examined, insufficient data are available to address whether intrinsic metabolic cycles underlie the two oscillations of circannual hibernation.Here we report results from an unbiased gas (GC) and liquid chromatography (LC)-mass spectroscopy (MS)-based metabolomic screen (12,26,38) comparing multiple individuals representing seven stages of the hibernator's circannual cycle. From a database containing 1,205 named compounds, 231 were identified in ground squirrel plasma.…”

mentioning

confidence: 99%

“…Here we report results from an unbiased gas (GC) and liquid chromatography (LC)-mass spectroscopy (MS)-based metabolomic screen (12,26,38) comparing multiple individuals representing seven stages of the hibernator's circannual cycle. From a database containing 1,205 named compounds, 231 were identified in ground squirrel plasma.…”

mentioning

confidence: 99%

Metabolic cycles in a circannual hibernator

Epperson¹,

Karimpour-Fard

Hunter

et al. 2011

Physiological Genomics

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nation as manifested in ground squirrels is arguably the most plastic and extreme of physiological phenotypes in mammals. Homeostasis is challenged by prolonged fasting accompanied by heterothermy, yet must be facilitated for survival. We performed LC and GC-MS metabolomic profiling of plasma samples taken reproducibly during seven natural stages of the hibernator's year, three in summer and four in winter (each n Ն 5), employing a nontargeted approach to define the metabolite shifts associated with the phenotype. We quantified 231 named metabolites; 106 of these altered significantly, demarcating a cycle within a cycle where torpor-arousal cycles recur during the winter portion of the seasonal cycle. A number of robust hibernation biomarkers that alter with season and winter stage are identified, including specific free fatty acids, antioxidants, and previously unpublished modified amino acids that are likely to be associated with the fasting state. The major pattern in metabolite levels is one of either depletion or accrual during torpor, followed by reversal to an apparent homeostatic level by interbout arousal. This finding provides new data that strongly support the predictions of a long-standing hypothesis that periodic arousals are necessary to restore metabolic homeostasis. Ictidomys tridecemlineatus; Spermophilus; ␥-glutamyl; biliverdin; NacetylA YEAR IN THE LIFE OF A HIBERNATOR begins with reproduction in spring, followed by growth in summer, and then massive storage of fat as fall approaches. Hibernation, characterized by months of fasting and dramatic oscillations between states of cold and warm body temperature (T b ), ensues only after adequate fat stores are deposited (7). Most of the fall and winter months are spent in a state of deep torpor in which metabolic, heart, and respiratory rates are reduced to Ͻ5% of their summer equivalents, and body temperature declines to as low as 0°C, or even below (5). However, all hibernating mammals spontaneously reverse torpor at regular intervals by elevating metabolic rate and employing strictly endogenous mechanisms of heat production including shivering and nonshivering thermogenesis. In the thirteen-lined ground squirrel, Ictidomys tridecemlineatus, elevated metabolic rate and T b (ϳ37°C) are maintained in each interbout arousal for ϳ10 -12 h before dropping again to initiate the next ϳ2 wk bout of torpor. Thus, the circannual hibernation rhythm can be viewed as a cycle between summer homeothermy and winter heterothermy, the latter of which is itself a cycle between torpor and arousal (see Fig. 1). These dramatic physiological shifts of hibernation have been postulated to result from intrinsic metabolic cycles (41) that may be revealed by metabolic profiling (42).Previous work to measure metabolite changes in hibernators documents a number of alterations in liver (2, 32, 36), brain (21, 40), brown adipose tissue (13), bile (4), and blood (1, 9, 24, 31) that begin to assess the metabolites cycling in association with hibernation. These data suggest a two-s...

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Analysis of the Adult Human Plasma Metabolome

Cited by 441 publications

References 24 publications

Oxylipid Profile of Low‐Dose Aspirin Exposure: A Pharmacometabolomics Study

Oxylipid Profile of Low‐Dose Aspirin Exposure: A Pharmacometabolomics Study

Plasma amino acid profiles in healthy East Asian subpopulations living in Japan

Metabolic cycles in a circannual hibernator

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