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 log2 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.

Macronutrient, Energy, and Bile Acid Metabolism Pathways Altered Following a Physiological Meal Challenge, Relative to Fasting, among Guatemalan Adults.

BACKGROUND: The healthy human metabolome, including its physiological responses after meal consumption, remains incompletely understood. One major research gap is the limited literature assessing how human metabolomic profiles differ between fasting and postprandial states after physiological challenges. OBJECTIVES: Our study objective was to evaluate alterations in high-resolution metabolomic profiles following a standardized meal challenge, relative to fasting, in Guatemalan adults. METHODS: We studied 123 Guatemalan adults without obesity, hypertension, diabetes, metabolic syndrome, or comorbidities. Every participant received a standardized meal challenge (520 kcal, 67.4 g carbohydrates, 24.3 g fat, 8.0 g protein) and provided blood samples while fasting and at 2 h postprandial. Plasma samples were assayed by high-resolution metabolomics with dual-column LC [C18 (negative electrospray ionization), hydrophilic interaction LC (HILIC, positive electrospray ionization)] coupled to ultra-high-resolution MS. Associations between metabolomic features and the meal challenge timepoint were assessed in feature-by-feature multivariable linear mixed regression models. Two algorithms (mummichog, gene set enrichment analysis) were used for pathway analysis, and P values were combined by the Fisher method. RESULTS: Among participants (62.6% male, median age 43.0 y), 1130 features (C18: 777; HILIC: 353) differed between fasting and postprandial states (all false discovery rate-adjusted q < 0.05). Based on differing C18 features, top pathways included: tricarboxylic acid cycle (TCA), primary bile acid biosynthesis, and linoleic acid metabolism (all Pcombined < 0.05). Mass spectral features included: taurine and cholic acid in primary bile acid biosynthesis; and fumaric acid, malic acid, and citric acid in the TCA. HILIC features that differed in the meal challenge reflected linoleic acid metabolism (Pcombined < 0.05). CONCLUSIONS: Energy, macronutrient, and bile acid metabolism pathways were responsive to a standardized meal challenge in adults without cardiometabolic diseases. Our findings reflect metabolic flexibility in disease-free individuals.