Acute caloric restriction acts on the plasma proteome and reveals Apolipoprotein C1 as a signal of nutritional state and metabolic disease

Abstract Caloric restriction (CR) has proven beneficial to healthspan and lifespan, but not enough is known about the molecular mechanisms that interlink the human CR response and its downstream effectors. We induced acute caloric restriction in a controlled human intervention study and compared plasma proteome, metabolome and endocrine responses. We report that plasma proteins that dominate the response to negative and positive energy balance in CR are associated with disease-relevant endocrine parameters in two population studies. For example, APOC1, a small and understudied apolipoprotein, was not only CR-induced but also dominated the human response to glucose consumption and differed in abundance between individuals with and without diabetes. Our study shows that acute and time-limited CR acts on the plasma proteome, affecting molecular pathways that are intrinsically associated with human endocrine parameters important for metabolic health.