Mapping Metabolic Organ Plasticity in Energy Adaptation

Condition(s) studied

Investigational drug(s) / intervention(s)

Calorie Restriction (CR): Participants in the CR group will be asked to stay on an energy deficit of 500 Kcal/day, based on their RMR measurement. This intervention is designed to optimize the likelihood that a substantial degree of CR is achieved through a variety of nutritional and behavioural strategies. The CR intervention will be conceptualized as an intensive behavioural approach coupled with dietary modifications and daily self-monitoring of calories, designed to promote adherence to long-term CR. Each participant will be provided with an individualized CR prescription for \~25% CR from baseline ad libitum energy intake as determined by intake as determined by their personalized RMR.

Time Restricted Eating (TRE): Participants in the TRE groups will be instructed at weekly personal meetings to consume all meals between 10am to 6pm, and to avoid consumption of food or caloric drinks during the fasting period (8 h eating window with 16 h of fasting).

Resistance Training (RT): The participants who are assigned to the RT groups will perform supervised and monitored RT three times a week for a duration of 10 weeks. During the first two weeks of training, participants will be familiarized with RT exercises to ensure adoption, adherence, and correction of their technique. Additionally, intensity will increase from 40-60% 1-repetition maximum (1RM). Guided training sessions will start with the evaluation of 10 RM. Participants will train for 60 minutes, 3 times a week, using a full-body workout with nine exercises for a major muscle group. The exercise sessions will last \~60 minutes and will include a five-minute warmup, followed by 50 minutes of resistance exercises, including nine upper- and lower-body exercises using weight-lifting machines. In every training session, subjects will complete between 8-12 repetitions. If subjects successfully finish three sets of 12 reps, extra weight will be added to maintain an increased intensity. The r

Study summary

Brief Summary (Plain Language)

Many people who lose weight experience a slowdown in their metabolism that is greater than expected. This response, called metabolic adaptation, makes it harder to continue losing weight or to keep weight off over time. The biological reasons for this slowdown are not fully understood.

Some organs in the body, especially the liver and kidneys, use a large amount of energy even when the body is at rest. Although these organs make up only a small portion of body weight, they account for a large share of daily energy use. Changes in the size or function of these organs may play an important role in metabolic adaptation, but this has not been well studied in humans.

The purpose of this study is to understand how different lifestyle approaches affect metabolic adaptation and the size of key metabolic organs. Specifically, the study compares three common strategies:

* resistance training without calorie restriction,
* a calorie-restricted diet, and
* time-restricted eating (eating all daily food within a limited time window).

Adults with overweight will take part in one of these approaches for 10 weeks. Before and after the study period, participants will undergo advanced measurements, including magnetic resonance imaging (MRI) scans to measure liver and kidney size, tests to measure resting metabolism, and assessments of body composition. Some participants will also undergo additional testing to measure daily energy use.

By understanding how different lifestyle strategies influence metabolism and organ size, this study aims to improve knowledge about why weight loss is difficult to maintain and to support the development of more personalized approaches to long-term weight management.

Eligibility

Primary outcome measure(s)

• Change in Metabolic Adaptation — Baseline to 10 weeks
  Change in metabolic adaptation, defined as the difference between predicted resting metabolic rate and measured resting metabolic rate. Measurement: Resting metabolic rate measured by indirect calorimetry and predicted from body composition-based equations.

Trial sites (1)

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