Metabolic profiles reflect weight loss maintenance and the composition of diet after very-low-energy diet

Background & aims: Diet and weight loss affect circulating metabolome. However, metabolite profiles induced by different weight loss maintenance diets and underlying longer term weight loss maintenance remain unknown. Herein, we investigated after-weight-loss metabolic signatures of two isocaloric 24-wk weight maintenance diets differing in satiety value due to dietary fibre, protein and fat contents and identified metabolite features that associated with successful weight loss maintenance. Methods: Non-targeted LC-MS metabolomics approach was used to analyse plasma metabolites of 79 women and men (mean age ± SD 49.7 ± 9.0 years; BMI 34.2 ± 2.5 kg/m2) participating in a weight management study. Participants underwent a 7-week very-low-energy diet (VLED) and were thereafter randomised into two groups for a 24-week weight maintenance phase. Higher satiety food (HSF) group consumed high-fibre, high-protein, and low-fat products, while lower satiety food (LSF) group consumed isocaloric low-fibre products with average protein and fat content as a part of their weight maintenance diets. Plasma metabolites were analysed before the VLED and before and after the weight maintenance phase. Metabolite features discriminating HSF and LSF groups were annotated. We also analysed metabolite features that discriminated participants who maintained ≥10% weight loss (HWM) and participants who maintained <10% weight loss (LWM) at the end of the study, irrespective of the diet. Finally, we assessed robust linear regression between metabolite features and anthropometric and food group variables. Results: We annotated 126 metabolites that discriminated the HSF and LSF groups and HWM and LWM groups (p < 0.05). Compared to LSF, the HSF group had lower levels of several amino acids, e.g. glutamine, arginine, and glycine, short-, medium- and long-chain acylcarnitines (CARs), odd- and even-chain lysoglycerophospholipids, and higher levels of fatty amides. Compared to LWM, the HWM group in general showed higher levels of glycerophospholipids with a saturated long-chain and a C20:4 fatty acid tail, and unsaturated free fatty acids (FFAs). Changes in several saturated odd- and even-chain LPCs and LPEs and fatty amides were associated with the intake of many food groups, particularly grain and dairy products. Increase in several (lyso)glycerophospholipids was associated with decrease in body weight and adiposity. Increased short- and medium-chain CARs were related to decreased body fat-free mass. Conclusions: Our results show that isocaloric weight maintenance diets differing in dietary fibre, protein, and fat content affected amino acid and lipid metabolism. Increased abundances of several phospholipid species and FFAs were related with greater weight loss maintenance. Our findings indicate common and distinct metabolites for weight and dietary related variables in the context of weight reduction and weight management. The study was registered in isrctn.org with identifier 67529475.