The impact of acute nutritional interventions on the plasma proteome

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Abstract

CONTEXT: Humans respond profoundly to changes in diet, while nutrition and environment have a great impact on population health. It is hence important to deeply characterise the human nutritional responses. OBJECTIVE: Endocrine parameters and the metabolome of human plasma are rapidly responding to acute nutritional interventions such as caloric restriction or a glucose challenge. It is less well understood whether the plasma proteome would be equally dynamic, and whether it could be a source of corresponding biomarkers. METHODS: We used high-throughput mass spectrometry to determine changes in the plasma proteome of i) ten healthy, young, male individuals in response to two days of acute caloric restriction followed by refeeding, ii) 200 individuals of the Ely epidemiological study before and after a glucose tolerance test at four time points (0, 30, 60, 120 minutes), and iii) 200 random individuals from the Generation Scotland study. We compare the proteomic changes detected to metabolome data as well as endocrine parameters. RESULTS: Both acute nutritional interventions, caloric restriction and the glucose challenge, substantially impacted the plasma proteome. Proteins responded across individuals or in an individual-specific manner. We identify nutrient-responsive plasma proteins that correlate with changes in the metabolome, as well as with endocrine parameters. In particular, our study highlights the role of apolipoprotein C1 (APOC1), a small, understudied apolipoprotein that was affected by caloric restriction and dominated the response to glucose consumption and differed in abundance between individuals with and without type 2 diabetes. CONCLUSION: Our study identifies APOC1 as a dominating nutritional responder in humans, and highlights the interdependency of acute nutritional response proteins and the endocrine system.

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