Low-Protein Meal Challenge as a Predictor for Weight Loss Success in Severe Obesity

Inter-individual variability in adaptive energy expenditure is a central determinant of weight-loss response. The established thrifty/spendthrift phenotyping protocols to identify weight loss resistant and susceptible metabolic phenotypes, respectively, rely on prolonged fasting and overfeeding using whole-room calorimetry assessments, which represents a substantial barrier to the prospective implementation in routine obesity care. To establish a clinically applicable method for specific metabolic phenotyping, the conducted study evaluated resting metabolic rate (RMR) measurement before and after 24-hour fasting and a low-protein meal test (LPMT) overfeeding protocol using ventilated hood calorimetry. In addition, biosamples were collected for the analysis of potential biomarkers. Measurement of fasting-induced changes in RMR could not be confirmed as a suitable method to identify weight loss-resistant individuals in the present cohort. However, the LPMT was identified as a promising tool to predict outcomes of calorie restriction treatments in individuals suffering from severe obesity. Lower capability for DIT in response to the low-protein (1 %) test meal was significantly associated with less weight and fat mass reduction. Furthermore, the results indicate a single postprandial measurement of FGF21 following a high-caloric, low-protein test meal prior to starting a caloric restriction can be used as a blood-based biomarker for subsequent WL outcomes. A blunted postprandial response in FGF21 was shown to be predictive of reduced FM loss. The simplified determination of metabolic phenotypes using such accessible methods could facilitate implementation in clinical practice and contribute to the personalization of treatment approaches for obesity in the future.