Late Diet-Induced Thermogenesis Predicts Weight Loss Success During a Very-Low-Calorie Diet in Severe Obesity

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Introduction : Resting metabolic rate (RMR) and diet-induced thermogenesis (DIT) are key components of energy expenditure that influence weight regulation and display considerable interindividual variability. Prior research demonstrates that low-protein overfeeding can differentiate metabolic phenotypes, with “thrifty” individuals (weight-loss resistant) exhibiting a blunted DIT response compared to “spendthrift” individuals (weight-loss susceptible).([ 1 ] [ 2 ] [ 3 ] [ 4 ]) In the current study, we evaluated whether a low-protein meal test can similarly predict weight loss success after a long-term VLCD in a cohort of severely obese individuals. Methods : 23 Patients with severe obesity (n=14 female; BMI ø47.7±6.9 kg/m2; Age ø46±11 years; FM 53.44±6.25%; FFM 46.56±6.25%) from a 6-month multimodal obesity therapy program with a 12-week very-low-calorie-diet (VLCD) are included in the current study. At baseline, after a 3-day standardized diet and a 24-hour fast, RMR was measured using ventilated hood techniques and body composition was determined via air displacement plethysmography (BodPod). Patients then underwent a high-caloric, low-protein (1% protein) meal test individualized to 50% of measured RMR. Postprandial EE was recorded at 30, 60, 90, 120, 150, and 180 minutes, allowing for calculation of% diet-induced thermogenesis (DIT) and the incremental area under the curve (iAUC). Patients then initiated the VLCD phase (800 kcal/day), which included weekly body weight and monthly fat mass (FM) and fat-free mass (FFM) recordings. Linear regression and Pearson’s correlation analyses were performed to assess associations between total as well as early (30–90 min) and late (120–180 min) postprandial thermogenesis and subsequent weight and fat mass loss. Results : After 12 weeks of VLCD, mean weight loss was 18.24 kg (−13.0%), mean FM loss was 16.14 kg (−22.1%), and mean FFM loss was 1.13 kg (−2.3%). Higher DIT (mean 8,4%) correlated with more%weight loss (r=0.51, p=0.02) and%FM loss (r=0.54, p=0.01), but not with%FFM loss (p=0.55). When DIT was divided into early (0–90 min) and late (120–180 min) phases, higher late DIT was associated with more%weight loss (r=0.51, p=0.02) and%FM loss (r=0.61, p=0.004). By contrast, early DIT correlated only with%weight loss (r=0.49, p=0.03) and showed no relationship with%FM or%FFM loss. Similar findings for absolute weight, FM and FFM loss were obtained when using early/late iAUC adjusted for RMR. Conclusion : Higher DIT after a high-caloric low-protein meal, specifically during the late (120–180 min) period, was a significant predictor for successful weight and fat mass reduction after a 12-week VLCD in our cohort with severe obesity. These results suggest that a low-protein meal challenge may serve as an effective tool for predicting the outcomes of calorie-restriction treatments, thereby facilitating tailored interventions and personalized approaches in obesity therapy. Publication History Article published online: 28 May 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

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