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

BACKGROUND: Overweight and obesity is a growing health problem worldwide. The most effective strategy to reduce weight is energy restriction (ER). ER has been shown to be beneficial in disease prevention and it reduces chronic inflammation. Recent studies suggest that reducing the protein quantity of a diet contributes to the beneficial effects by ER. The organ most extensively affected during ER is white adipose tissue (WAT). OBJECTIVE: The first objective was to assess changes in gene expression between a high-protein diet and a normal protein diet during ER. Second, the total effect of ER on changes in gene expression in WAT was assessed. METHODS: In a parallel double-blinded controlled study, overweight older participants adhered to a 25% ER diet, either combined with high-protein intake (HP-ER, 1.7 g kg-1 per day), or with normal protein intake (NP-ER, 0.9 g kg-1 per day) for 12 weeks. From 10 HP-ER participants and 12 NP-ER participants subcutaneous WAT biopsies were collected before and after the diet intervention. Adipose tissue was used to isolate total RNA and to evaluate whole-genome gene expression changes upon a HP-ER and NP-ER diet. RESULTS: A different gene expression response between HP-ER and NP-ER was observed for 530 genes. After NP-ER, a downregulation in expression of genes linked to immune cell infiltration, adaptive immune response and inflammasome was found, whereas no such effect was found after HP-ER. HP-ER resulted in upregulation in expression of genes linked to cell cycle, GPCR signalling, olfactory signalling and nitrogen metabolism. Upon 25% ER, gene sets related to energy metabolism and immune response were decreased. CONCLUSIONS: Based on gene expression changes, we concluded that consumption of normal protein quantity compared with high-protein quantity during ER has a more beneficial effect on inflammation-related gene expression in WAT.