The impact of protein quantity during energy restriction on genome-wide gene expression analysis in human adipose tissue

Bussel, Inge van; Backx, Evelien; Groot, Lisette de; Tieland, Michael; Afman, Lydia


Overweight is a growing health problem worldwide. The most effective strategy to reduce weight is energy restriction (ER): restriction of food intake without malnutrition. ER has been shown to be beneficial in disease prevention, healthy aging, and inflammation. Recent studies suggest that reducing the protein content of a diet contributes to the beneficial effects by ER. The first objective of our study was to assess the effect of energy restriction on changes in gene expression in adipose tissue. Secondly, the changes in gene expression were compared between a high protein diet and a normal protein diet during energy restriction. In a parallel double-blinded study, overweight older subjects adhered to a 25% ER diet, either combined with high protein intake (HP-ER, 1.7 g/kg per day), or with normal protein intake (NP-ER, 0.9 g/kg per day) for 12 weeks. From 10 HP-ER subjects and 12 NP-ER subjects subcutaneous adipose tissue biopsies were collected before and after the diet. Adipose tissue was used to isolate total RNA and to evaluate whole genome gene expression changes upon a HP-ER and NP-ER diet. Upon 25% ER, clusters of gene sets in energy metabolism, such as lipid metabolism and PPARα targets, NRF2 targets, glucose metabolism, and TCA cycle, as well as gene sets in oxidative phosphorylation, adaptive immune response, immune cell infiltration, and cell cycle were decreased, and RNA translation and processing gene sets were increased. A different gene expression response between HP-ER and NP-ER was observed for 530 genes. Pathway analysis revealed that after NP-ER a downregulation in expression of genes involved in adaptive immune response was present. HP-ER resulted in an upregulation of pathways involved in cell cycle, GPCR signalling, olfactory signalling and nitrogen metabolism. Based on the gene expression changes, we concluded that HP seems to be less beneficial for ER’s effect on immune-related gene expression in adipose tissue.