Mapping Metabolic Organ Plasticity in Energy Adaptation (MAP)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Energy Metabolism; Overweight , Obesity
• Intervention / Treatment: Behavioral: Calorie Restriction (CR); Behavioral: Resistance Training (RT); Behavioral: Time Restricted Eating (TRE)

Detailed Description

Metabolic adaptation refers to a reduction in resting energy expenditure that is greater than what would be predicted from changes in body weight or body composition. This phenomenon is commonly observed during weight loss and is believed to contribute to weight regain. While metabolic adaptation is well documented, the underlying physiological mechanisms remain unclear.

Highly metabolic organs, including the liver and kidneys, consume a disproportionate amount of energy at rest. Emerging evidence suggests that reductions in the size of these organs during energy deficit states may contribute to declines in resting metabolic rate. However, few human studies have directly examined how different lifestyle interventions influence organ size and how these changes relate to metabolic adaptation.

This study is a 10-week, open-label, lifestyle intervention trial conducted in sedentary adults with overweight. Participants are assigned to one of three intervention groups: resistance training with a normal diet, calorie restriction, or time-restricted eating. All participants are supervised by qualified health professionals throughout the study.

Measurements are conducted before and after the intervention period and include gold-standard assessments of resting metabolic rate, body composition, liver and kidney volume using MRI, and hepatic fat content. A subset of participants undergoes doubly labeled water testing to assess total daily energy expenditure.

The primary goal of the study is to compare the degree of metabolic adaptation across the three lifestyle strategies. Secondary objectives include evaluating changes in liver and kidney volume and determining how these organ-level changes contribute to changes in metabolism. The study is designed to provide mechanistic insight into how exercise- and diet-based interventions influence energy regulation at the organ level.

The results of this research are expected to advance understanding of metabolic adaptation in humans and may help inform more effective and individualized strategies for weight loss and long-term weight maintenance.

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Tel Aviv, Israel, 69978
    • Sylvan Adams Sport Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Sedentary men and women aged 25-60 years
• Body mass index (BMI) of 25-35 kg/m²

Exclusion Criteria:

• Participation in another exercise or weight loss program in the last 6 months
• Non-stable weight (>±5%) over the past 6 months
• Smoking within the past 6 months
• Post-menopause
• Breastfeeding
• Pregnancy or having been pregnant within the past 6 months
• Contraindication for MRI scans (e.g., tattoos, intrauterine devices, permanent makeup, etc.)
• Severe cardiopulmonary disease (e.g., recent myocardial infarction or unstable angina)
• Musculoskeletal or neuromuscular impairments that preclude exercise training
• Cognitive impairments
• Other health issues, including cancer, diabetes, thyroid disease, hypertension, or chronic renal failure
• Use of drugs that affect body metabolism
• Secondary liver disease (viral, autoimmune, alcoholic, or hepatotoxic)
• Alcohol consumption above 20 g/day for women or 30 g/day for men

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Calorie Restriction; energy deficit of 500 Kcal/day	Behavioral: 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.
Experimental: Time Restricted Eating; fasting period (8 h eating window with 16 h of fasting).	Behavioral: 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
Experimental: Resistance Training; Participants will train for 60 minutes, 3 times a week, using a full-body workout with nine exercises for a major muscle group.	Behavioral: 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Metabolic Adaptation	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.	Baseline to 10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Resting Metabolic Rate (RMR)	Change in resting metabolic rate. Measurement: Resting metabolic rate (kcal/day) measured by indirect calorimetry.	Baseline to 10 weeks
Change in Liver Volume	Change in liver volume following the intervention. Measurement: Liver volume (cm³) measured by magnetic resonance imaging (MRI).	Baseline to 10 weeks
Change in Kidney Volume	Change in total kidney volume. Measurement: Left and right kidney volume (cm³) measured by magnetic resonance imaging (MRI).	Baseline to 10 weeks
Association Between Organ Volume Changes and Metabolic Adaptation	Relationship between changes in liver and kidney volume and changes in metabolic adaptation. Measurement: Correlation between MRI-derived organ volume changes and metabolic adaptation values.	Baseline to 10 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Total Daily Energy Expenditure	Change in total daily energy expenditure in a subset of participants. Measurement: Total daily energy expenditure measured by doubly labeled water.	Baseline to 10 weeks
Change in Body Composition	Change in body fat-free mass. Measurement: Body composition measured by dual-energy X-ray absorptiometry (DXA) or bioelectrical impedance analysis when DXA is unavailable.	Baseline to 10 weeks

Collaborators and Investigators

• Sponsor: Tel Aviv University

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: February 9, 2026
• First Submitted That Met QC Criteria: February 15, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 15, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Energy expenditure; weight loss; Metabolic adaptation; Metabolic organs; lifestyle modalities
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Body Weight Changes; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Weight Loss; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Therapeutics; Physical Therapy Modalities; Diet, Food, and Nutrition; Physiological Phenomena; Nutritional Physiological Phenomena; Patient Care; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Diet Therapy; Nutrition Therapy; Diet; Physical Conditioning, Human; Exercise; Energy Intake; Resistance Training; Caloric Restriction
• Other Study ID Numbers: 0003858-5

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No