Metabolomic Profile Responses to a Standardized Meal Challenge Differ by Cardiometabolic Disease Status

Abstract

Abstract Objectives Metabolic flexibility is the physiologic adaptation to differing energy availability and requirement states, such as during meal consumption. Metabolic inflexibility is definitional of some cardiometabolic diseases (CMDs), however the metabolomic profile response (metabolomic flexibility) after meal consumption, relative to a fasting state, in CMDs remains unclear. We compared metabolomic flexibility following consumption of a standardized meal challenge among adults with or without CMDs. Methods Study participants (n = 349; 37–54 years, 55% female) received a standardized meal challenge (520 kcal, 67.4 g carbohydrates, 24.3 g fat, 8.0 g protein; 259 mL). Blood samples were collected at baseline and two hours post-challenge. Plasma samples were assayed by high-resolution metabolomic profiling with dual column liquid chromatography (carbon 18 (C18], negative electrospray ionization; hydrophilic interaction liquid chromatography [HILIC], positive electrospray ionization) coupled to ultra-high-resolution mass spectrometry. Participants were categorized by obesity, hypertension, diabetes and metabolic syndrome. Metabolome-wide associations between features and meal challenge timepoint were assessed in feature-by-feature multivariate generalized linear regression models, including disease profile, age, and sex. Results Two hundred and twenty-six participants (65%) had at least one of the four CMDs: 33% were considered obese, 6% had diabetes, 39% had hypertension, and 50% had metabolic syndrome. Log2-normalized ratios of feature peak areas (post-prandial: fasting) clustered separately among participants with versus without any CMDs. Among participants with CMDs, the meal challenge altered >1700 feature peak areas (all q < 0.05). In individuals without CMDs, the meal challenge changed >1100 feature peak areas (all q < 0.05). The response to the meal challenge of > 100 feature peak areas (C18, HILIC) differed by CMD status (all P < 0.05). These features included dipeptides, lipids (carnitines, glycerophospholipids), and a bile acid metabolite (all P < 0.05). Conclusions Compared to individuals without CMDs, macronutrient metabolism following a standardized meal challenge differed among those with CMDs, reflecting altered metabolic flexibility. Funding Sources National Institutes of Health.