Plasma phospholipids, non-esterified plasma polyunsaturated fatty acids and oxylipids are associated with BMI C. Austin Pickens a , Lorraine M. Sordillo b , Sarah S. Comstock a , William S. Harris c , Kari Hortos d , Bruce Kovan d,e , Jenifer I. Fenton a,n a Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, USA b College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA c Sanford School of Medicine, The University of South Dakota, Sioux Falls, SD, USA d College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA e Tri-County Gastroenterology Professional Corporation, Clinton Tri-County Gastroenterology Professional Corporation, MI, USA article info Article history: Received 6 October 2014 Received in revised form 1 December 2014 Accepted 2 December 2014 Keywords: Lipidome Obesity Human Biomarker Inflammation Nervonic acid abstract The obese lipid profile is associated with increased free fatty acids and triacylglycerides. Currently, little is known about the plasma lipid species associated with obesity. In this study, we compared plasma lipid fatty acid (FA) profiles as a function of BMI. Profiling phospholipid (PL) FAs and their respective oxylipids could predict which obese individuals are more likely to suffer from diseases associated with chronic inflammation or oxidative stress. We investigated the relationship between BMI and plasma PL (PPL) FA composition in 126 men using a quantitative gas chromatography analysis. BMI was inversely associated with both PPL nervonic and linoleic acid (LA) but was positively associated with both dihomo-γ-linolenic and palmitoleic acid. Compared to lean individuals, obese participants were more likely to have ω-6 FAs, except arachidonic acid and LA, incorporated into PPLs. Obese participants were less likely to have EPA and DHA incorporated into PPLs compared to lean participants. Non-esterified plasma PUFA and oxylipid analysis showed ω-6 oxylipids were more abundant in the obese plasma pool. These ω-6 oxylipids are associated with increased angiogenesis (i.e. epoxyeicosatrienoates), reactive oxygen species (i.e. 9-hydroxyeicosatetraenoate), and inflammation resolution (i.e. Lipoxin A4). In summary, BMI is directly associated with specific PPL FA and increased ω-6 oxylipids. & 2014 Elsevier Ltd. All rights reserved. 1. Introduction Obesity is associated with chronic low-grade inflammation, incr- eased oxidative stress, insulin resistance, and metabolic dysregulation [1]. These conditions are linked to excess lipid storage in white adipose tissue (WAT). This increased lipid accumulation places demands on WAT causing macrophage polarization [2], altered adipokine secretion [3], and increased inflammation. The lipid profile (i.e. lipidome), incl- uding oxygenated FA metabolites deemed oxylipids, can influence production of inflammatory cytokines [4]. Obesity is associated with dietary shifts in FA intake [5], which alters FA composition of cellular phospholipid (PL) membranes and plasma PLs (PPLs) [6]. PUFAs within membrane PLs serve as substrates for the biosynthesis of oxylipids through either enzymatic or non-enzymatic pathways. Thus, obesity- induced changes in fatty acid concentrations or metabolism will gre- atly impact the character of the inflammatory response. Therefore, the plasma lipidome, which is indicative of dietary FA intake and changes in FA metabolism, may contain potential biomarkers of the subclinical chronic inflammation associated with obesity. Although obesity is typically associated with inflammation, many lipid metabolites, including PUFA-derived resolvins and protectins, are Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/plefa Prostaglandins, Leukotrienes and Essential Fatty Acids http://dx.doi.org/10.1016/j.plefa.2014.12.001 0952-3278/& 2014 Elsevier Ltd. All rights reserved. Abbreviations: AA, arachidonic acid; ALA, alpha-linolenic acid; BHT, butylated hydroxytoluene; COX, cyclooxygenase; D5D, delta-5-desaturase; D6D, delta-6- desaturase; DGLA, dihomo-γ-linolenic acid; DiHETE, dihydroxy eicosatetraenoate; DPA, docosapentaenoic acid; DTA, docosatetraenoic acid; EET, epoxy eicosatrieno- ate; EpDPE, epoxy docosapentaenoate; EpODE, epoxy octadecadienoate; ETE, epoxy eicosatetraenoate; FAMEs, fatty acid methyl esters; HDoHE, hydroxy docosahex- aenoate; HETE, hydroxy eicosatetraenoate; HMW, high molecular weight adipo- nectin; HODE, hydroxy octadecadienoate; IL-6, interleukin-6; LA, linoleic acid; LMW, low molecular weight adiponectin; LOD, limit of detection; LTA4, leukotriene A4; LOX, lipoxygenase; LXA4, lipoxin A4; MCP-1, monocyte chemoattractant protein-1; MetS, metabolic syndrome; MMW, medium molecular weight adipo- nectin; MRM, multiple reaction monitoring; NF-κB, nuclear factor kappa of activated B cells; ODE, octadecadienoate; OR, odds ratio; PGE, prostaglandin E-series; PL, phospholipid; PPAR-γ, peroxisome proliferator-activated receptor gamma; PPL, plasma phospholipid; RvD, resolvin D-series; SatFAs, saturated fatty acids; SatFFAs, saturated free fatty acids; TNF-α, tumor necrosis factor alpha; WAT, white adipose tissue; ω-3, omega-3; ω-6, omega-6 n Correspondence to: 469 Wilson Rd, Rm 208B, Michigan State University, East Lansing, MI 48824, USA. Tel.: þ1 517 353 3342; fax: þ1 517 353 8963. E-mail address: imigjeni@msu.edu (J.I. Fenton). Prostaglandins, Leukotrienes and Essential Fatty Acids 95 (2015) 31–40