Metabolomic Profiling Demonstrates Postprandial Changes in Fatty Acids and Glycerophospholipids Are Associated with Fasting Inflammation in Guatemalan Adults

Background: Metabolic flexibility is the responsiveness to heterogeneous physiological conditions, such as food ingestion. A key unresolved question is how inflammation affects metabolic flexibility. Objectives: Our study objective was to compare metabolic flexibility, specifically the metabolomic response to a standardized meal, by fasting inflammation status. Methods: Participants in Guatemala (n = 302, median age 44 y, 43.7% men) received a standardized, mixed-macronutrient liquid meal. Plasma samples (fasting, 2 h postmeal) were assayed by dual-column LC [reverse phase (C18) and hydrophilic interaction LC (HILIC)] with ultra-high-resolution MS, for concentrations of 6 inflammation biomarkers: high-sensitivity C-reactive protein (hsCRP), leptin, resistin, IL-10, adiponectin, and soluble TNF receptor II (TNFsR). We summed the individual inflammation biomarker z-scores, after reverse-coding of anti-inflammation biomarkers. We identified features with peak areas that differed between fasting and postmeal (false discovery rate-adjusted q <0.05) and compared median log(2) postprandial/fasting peak area ratios by inflammation indicators. Results: We found 1397 C18 and 974 HILIC features with significant postprandial/fasting feature ratios (q <0.05). Overall inflammation z-score was directly associated with the postprandial/fasting feature ratios of arachidic acid, and inversely associated with the feature ratio of lysophosphatidic acid (LPA), adjusting for age and sex (all P < 0.05). The postprandial/fasting ratio of arachidic acid was negatively correlated with resistin, IL-10, adiponectin, and TNFsR concentrations (all P < 0.05). Feature ratios of several fatty acids-myristic acid [m/z 227.2018, retention time (RT) 229], heptadecanoic acid (m/z 269.2491, RT 276), linoleic acid (m/z 280.2358, RT 236)-were negatively correlated with fasting plasma concentrations of leptin (nanograms per milliliter) and adiponectin (micrograms per milliliter), respectively (all P < 0.05). The postprandial/fasting ratio of LPA was positively correlated with IL-10 and adiponectin (both P < 0.05); and the ratio of phosphatidylinositol was positively correlated with hsCRP (P < 0.05). Conclusions: Postprandial responses of fatty acids and glycerophospholipids are associated with fasting inflammation status in adults in Guatemala.