Metabolomic Profiling Demonstrates Postprandial Changes in Saturated Fatty Acids and Glycerophospholipids Are Associated With Fasting Inflammation

Abstract

ObjectivesMetabolic flexibility is the responsiveness to heterogeneous physiologic conditions, such as food ingestion. A key unresolved question is how inflammation affects metabolic flexibility. Our study objective was to compare metabolic flexibility, specifically the metabolomic response to a standardized meal, by fasting inflammation status, among Guatemalan adults. MethodsParticipants (n = 302, median age 44 years, 43.7% men) received a standardized, mixed-macronutrient liquid meal. Plasma samples (fasting, 2 hr post-meal) were assayed by dual column liquid chromatography (reverse phase [C18] and hydrophilic interaction liquid chromatography [HILIC]) with ultra-high resolution mass spectrometry, and for concentrations of 6 inflammation biomarkers (hsCRP, leptin, resistin, IL-10, adiponectin, TNFsR). We summed the 6 fasting inflammation biomarker Z-scores, after reverse-coding of anti-inflammation biomarkers. For feature selection, we identified features with peak areas differing between fasting and post-meal (FDR-adjusted q < 0.05) and compared median log2 postprandial/fasting peak area ratios by inflammation indicators. Results1,397 C18 and 967 HILIC features had significant log2 postprandial/fasting peak area ratios (q < 0.05). These log2 feature peak area ratios clustered differentially between people in the lowest tertile vs higher 2 tertiles of the inflammation index. The inflammation index was directly associated with log2 ratios of arachidic acid, and inversely associated with log2 ratios of caproic acid and lysophosphatidic acid, adjusting for age and sex (all P < 0.05). The log2 ratio of arachidic acid was negatively correlated with resistin, IL-10, adiponectin, and TNFsR concentrations (all P < 0.05). The log2 ratio of caproic acid was positively correlated with adiponectin and IL-10 concentrations, and negatively correlated with hsCRP concentration (all P < 0.05). The log2 ratio of lysophosphatidic acid was positively correlated with IL-10 and adiponectin, and log2 ratio of phosphatidylinositol was positively correlated with hsCRP (all P < 0.05). ConclusionsOur findings showed that postprandial responses of saturated fatty acids and glycerophospholipids were associated with fasting inflammation. Funding SourcesNational Institutes of Health (HD075784, HL007745).