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Diet-induced Weight Loss and Phenotypic Flexibility Among Healthy Overweight Adults: A Randomized Trial
Journal article   Open access   Peer reviewed

Diet-induced Weight Loss and Phenotypic Flexibility Among Healthy Overweight Adults: A Randomized Trial

Milena Rundle, Jarlei Fiamoncini, E Louise Thomas, Suzan Wopereis, Lydia A. Afman, Lorraine Brennan, Christian A. Drevon, Thomas E. Gundersen, Hannelore Daniel, Isabel Garcia Perez, …
The American journal of clinical nutrition, Vol.118(3), pp.591-604
2023
DOI: https://doi.org/10.1016/j.ajcnut.2023.07.002
PMID: 37661105
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Published (Version of Record) Open Access CC BY V4.0

Abstract

insulin sensitivity meal challenges metabolites phenotypic flexibility weight loss
Background The capacity of an individual to respond to changes in food intake so that postprandial metabolic perturbations are resolved, and metabolism returns to its pre-prandial state, is called phenotypic flexibility. This ability may be a more important indicator of current health status than metabolic markers in a fasting state. Aim In this parallel randomized controlled trial study, an energy-restricted healthy diet and 2 dietary challenges were used to assess the effect of weight loss on phenotypic flexibility. Methods Seventy-two volunteers with overweight and obesity underwent a 12-wk dietary intervention. The participants were randomized to a weight loss group (WLG) with 20% less energy intake or a weight-maintenance group (WMG). At weeks 1 and 12, participants were assessed for body composition by MRI. Concurrently, markers of metabolism and insulin sensitivity were obtained from the analysis of plasma metabolome during 2 different dietary challenges—an oral glucose tolerance test (OGTT) and a mixed-meal tolerance test. Results Intended weight loss was achieved in the WLG (−5.6 kg, P < 0.0001) and induced a significant reduction in total and regional adipose tissue as well as ectopic fat in the liver. Amino acid-based markers of insulin action and resistance such as leucine and glutamate were reduced in the postprandial phase of the OGTT in the WLG by 11.5% and 28%, respectively, after body weight reduction. Weight loss correlated with the magnitude of changes in metabolic responses to dietary challenges. Large interindividual variation in metabolic responses to weight loss was observed. Conclusion Application of dietary challenges increased sensitivity to detect metabolic response to weight loss intervention. Large interindividual variation was observed across a wide range of measurements allowing the identification of distinct responses to the weight loss intervention and mechanistic insight into the metabolic response to weight loss.

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UN Sustainable Development Goals (SDGs)

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