Mechanisms of weight maintenance under high- and low-protein, low-glycaemic index diets

Scope: Weight maintenance after intended weight loss is a challenge in an obesogenic environment. In a large multicentre dietary intervention study (DiOGenes), it has recently been demonstrated that a high‐protein/low‐glycaemic index (HP/LGI) diet was slightly more efficient in maintaining weight loss than low‐protein/LGI or high‐GI (LP/LGI or HGI) diets. Here, we use a proteomic approach to assess the molecular mechanisms behind this positive effect. Methods and results: A subset of the most successful (weight loser, n=12) and unsuccessful (weight re‐gainer, n=12) individuals consuming the LGI diets with either high‐ or low‐protein content (HP or LP/LGI), following an initial calorie deficit run‐in weight loss phase, were analyzed at the plasma protein level. Proteomic analysis revealed 18 proteins regulated after 6 months of the dietary weight maintenance phase. Furthermore, 12 proteins were significantly regulated as a function of success rate under an HP diet, arising as candidate biomarkers of mechanisms of successful weight maintenance under an HP/LGI diet. Pregnancy‐zone protein (PZP) and protein S (PROS1) were revealed as novel biomarkers of weight maintenance showing opposite effects. Conclusion: Semantic network analysis of the 12 regulated proteins revealed that under an HP/LGI an anti‐atherogenic effect and alterations of fat metabolism were associated with the success of maintaining the initial weight loss.