Triacylglycerol Fatty Acid Composition in Diet-Induced Weight Loss in Subjects with Abnormal Glucose Metabolism – the GENOBIN Study Ursula Schwab 1,2 *, Tuulikki Seppa ¨ nen-Laakso 3 , Laxman Yetukuri 3 , Jyrki A ˚ gren 4 , Marjukka Kolehmainen 1 , David E. Laaksonen 4,5 , Anna-Liisa Ruskeepa ¨a ¨ 3 , Helena Gylling 1,2 , Matti Uusitupa 1 , Matej Ores ˇic ˇ 3 * for the GENOBIN Study Group 1 School of Public Health and Clinical Nutrition, Department of Clinical Nutrition and Food and Health Research Centre, University of Kuopio, Kuopio, Finland, 2 Kuopio University Hospital, Kuopio, Finland, 3 VTT Technical Research Centre of Finland, Espoo, Finland, 4 Department of Physiology, University of Kuopio, Kuopio, Finland, 5 Department of Medicine, Kuopio University Hospital, Kuopio, Finland Abstract Background: The effect of weight loss on different plasma lipid subclasses at the molecular level is unknown. The aim of this study was to examine whether a diet-induced weight reduction result in changes in the extended plasma lipid profiles (lipidome) in subjects with features of metabolic syndrome in a 33-week intervention. Methodology/Principal Findings: Plasma samples of 9 subjects in the weight reduction group and 10 subjects in the control group were analyzed using mass spectrometry based lipidomic and fatty acid analyses. Body weight decreased in the weight reduction group by 7.862.9% (p,0.01). Most of the serum triacylglycerols and phosphatidylcholines were reduced. The decrease in triacylglycerols affected predominantly the saturated short chain fatty acids. This decrease of saturated short chain fatty acid containing triacylglycerols correlated with the increase of insulin sensitivity. However, levels of several longer chain fatty acids, including arachidonic and docosahexanoic acid, were not affected by weight loss. Levels of other lipids known to be associated with obesity such as sphingolipids and lysophosphatidylcholines were not altered by weight reduction. Conclusions/Significance: Diet-induced weight loss caused significant changes in global lipid profiles in subjects with abnormal glucose metabolism. The observed changes may affect insulin sensitivity and glucose metabolism in these subjects. Trial Registration: ClinicalTrials.gov NCT00621205 Citation: Schwab U, Seppa ¨nen-Laakso T, Yetukuri L, A ˚ gren J, Kolehmainen M, et al. (2008) Triacylglycerol Fatty Acid Composition in Diet-Induced Weight Loss in Subjects with Abnormal Glucose Metabolism – the GENOBIN Study. PLoS ONE 3(7): e2630. doi:10.1371/journal.pone.0002630 Editor: Ulf Rise ´rus, Uppsala University, Sweden Received December 12, 2007; Accepted June 10, 2008; Published July 9, 2008 Copyright: ß 2008 Schwab et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The study was financially supported by grants from Sigrid Juselius foundation, the Academy of Finland (no. 209445, no. 211497), and EVO funding (no. 5179, no. 5198). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: ursula.schwab@uku.fi (US); matej.oresic@vtt.fi (MO) Introduction Dyslipidemia and abnormal fatty acid metabolism - elongation and desaturation - are characteristic in obesity, especially in association with the metabolic syndrome and abnormal glucose metabolism, i.e. impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) [1]. Weight loss improves the serum lipid profile in part by decreasing the concentration of serum triacylglycerols (TG) and increasing HDL cholesterol and HDL/LDL ratio in an antiatherogenic direction [2–4]. The effect of weight loss on specific plasma lipid molecular subclasses is not well understood. Such information may be valuable to elucidate specific lipid species that directly or indirectly affect insulin sensitivity. For example, elevated flux of saturated fatty acids (e.g., palmitic or stearic acid) into peripheral tissues may lead to production of lipotoxic metabolites in peripheral tissues [5– 7]. Changes in the fatty acid composition of TG, the major carriers of fatty acids to peripheral tissues, may therefore alter the risk for developing lipotoxicity-related complications. Obesity and insulin resistance are associated with impaired elongation and desaturation of fatty acids, reflected in the serum by, e.g., higher proportions of myristic and palmitic acid and lower proportions of longer-chain n-6 and n-3 fatty acids [8,9]. Such an adverse fatty acid profile has also predicted worsening insulin resistance, hyperglycemia and T2DM in prospective cohort studies [10–12]. Diet-induced weight loss has resulted in desaturation and elongation of serum and tissue fatty acids in addition to an improvement in insulin sensitivity [13]. Sphingomyelin, a marker of abnormal sphingolipid metabolism and a possible risk factor in atherosclerosis [14], has also been elevated in an obese mouse model [15]. Lysophosphatidylcholines PLoS ONE | www.plosone.org 1 July 2008 | Volume 3 | Issue 7 | e2630