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Title:   Author  item
                                            CAJKA, TOMAS - University Of Californiaitem
                                            DAVIS, RYAN - Metabolon, Incitem
                                            AUSTIN, KATHRYN - University Of Californiaitem
                                            Newman, Johnitem
                                            GERMAN, J BRUCE - University Of Californiaitem
                                            FIEHN, OLIVER - University Of Californiaitem
                                            SMILOWITZ, JENNIFER - University Of California
  Submitted to: Metabolomics
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 6/21/2016
                                    Publication  Date: 7/12/2016
                                    Citation: Cajka, T., Davis, R., Austin, K.J., Newman, J.W., German, J., Fiehn, O., Smilowitz, J.T. 2016. Using a lipidomics approach for nutritional phenotyping in response to a test meal containing gamma-linolenic acid. Journal of Proteome Research. 12:127. doi: 10.1007/s11306-016-1075-9.Interpretive Summary: Plasma fatty acids come preformed in the diet, and are made by the body through the action of enzymes that remove hydrogens to make double bonds or add carbons to elongate the fatty acid chains. This study was designed to examine the elongation of gamma linolenic acid (GLA), an eighteen carbon fatty acid with 3 double bounds (i.e. 18:3n6) into dihomo-gamma-linolenic acid (DGLA), a twenty carbon fatty acid with three double bonds (i.e. 20:3n6) over an eight-hour period.  To do this, both targeted and untargeted analytical approaches were used.  In a single blind, placebo-controlled, crossover design, seven healthy subjects consumed a test meal that consisted of gamma-linolenic acid (GLA) or a control fat on three separate test days each. Total plasma fatty acid concentrations and 366 unique lipid species were measured at 0, 2, 4, 6 and 8 h in response to the test meals. Mean plasma GLA was 7-fold higher to the GLA challenge compared with baseline and the control meal. By 8 h, mean plasma DGLA was significantly higher in response to the GLA test meal than baseline and the control group. Five of the seven subjects were “responders” in converting GLA into DGLA, but two subjects did not show this conversion. Using polyunsaturated fatty acid metabolism as an example, this study demonstrates between-subject differences in the ability to synthesize nutritionally important molecules, and such metabolic phenotyping may have uses in providing individual dietary and medicinal recommendations.
                                Technical Abstract: Plasma fatty acids are derived from preformed sources in the diet and de novo synthesis through the action of desaturase and elongase enzymes. This study was designed to examine the elongation of 18:3n6 into 20:3n6 over an eight-hour period using both targeted gas chromatography–flame ionization detection and untargeted liquid chromatography–mass spectrometry-based lipidomics. In a single blind, placebo-controlled, crossover design, seven healthy subjects consumed a test meal that consisted of gamma-linolenic acid (GLA) or a control fat on three separate test days each. Total plasma fatty acid concentrations and 366 unique lipid species were measured at 0, 2, 4, 6 and 8 h in response to the test meals. Mean plasma 18:3n6 was 7-fold higher to the GLA challenge compared with baseline and the control meal. By 8 h, mean plasma 20:3n6 was significantly higher in response to the GLA test meal than baseline and the control group. Five of the seven subjects were “responders” in converting GLA into DGLA, but two subjects did not show this conversion. Using polyunsaturated fatty acid metabolism as an example, this study demonstrates inter-individual differences in enzymatic capacities to inform exact nutritional and metabolic phenotyping that could be used for precision medicine.


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