Weight Loss Composition and Metabolic Adaptation During Hypocaloric Dieting

The Relationship Between Weight Loss Composition, Body Composition Changes, and Metabolic Adaptation During a Hypocaloric Dietary Intervention

Weight loss induced by hypocaloric dietary interventions is commonly accompanied by reductions in resting metabolic rate (RMR), a phenomenon often described as metabolic adaptation. The magnitude of this decline varies substantially between individuals and may depend not only on the amount of weight lost but also on the composition of weight loss, particularly the relative contributions of fat mass and fat-free mass.

This prospective interventional study will investigate whether changes in body composition during a hypocaloric dietary intervention are associated with changes in RMR and metabolic adaptation. Approximately 150 adults with overweight or obesity will participate in a structured dietary program designed to induce moderate energy restriction. Body composition and resting metabolic rate will be assessed before and after the intervention to evaluate associations between fat mass loss, fat-free mass loss, and metabolic responses to weight reduction.

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity
• Intervention / Treatment: Behavioral: Hypocaloric Diet

Detailed Description

Weight loss achieved through caloric restriction is consistently associated with reductions in resting metabolic rate (RMR). In many individuals, the decrease in energy expenditure exceeds what would be predicted from the loss of body mass or body composition alone, a phenomenon commonly described as metabolic adaptation or adaptive thermogenesis. This response has been proposed as one potential contributor to the difficulty many individuals experience in maintaining weight loss over time.

Fat-free mass is the primary determinant of resting energy expenditure because it includes metabolically active tissues such as skeletal muscle and organs. Consequently, the relative proportion of fat mass and fat-free mass lost during weight reduction may influence the magnitude of RMR decline. Dietary strategies that promote preservation of fat-free mass, such as adequate protein intake and engagement in physical activity, may attenuate metabolic slowing during weight loss. However, substantial inter-individual variability in metabolic responses to weight loss has been reported, and the role of weight-loss composition in shaping these responses remains incompletely understood.

The present study aims to examine the relationship between changes in body composition and changes in resting metabolic rate during a structured hypocaloric dietary intervention in adults with overweight or obesity. Participants will follow individualized dietary plans designed to produce a moderate energy deficit. Body composition will be assessed using dual-energy X-ray absorptiometry (DXA), and resting metabolic rate will be measured using indirect calorimetry at baseline and following completion of the intervention. Anthropometric measures and physical activity patterns will also be recorded.

By evaluating the relative contributions of fat mass loss and fat-free mass loss to changes in energy expenditure, this study aims to improve understanding of the physiological responses to weight reduction. The findings may help inform weight-loss strategies designed to minimize unfavorable metabolic adaptations and support more sustainable long-term weight management.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yftach Prof. Gepner, PhD; Phone Number: +972 50-682-8501; Email: gepner@tauex.tau.ac.il
• Study Contact Backup: Name: Lien Bruck; Phone Number: +972 587487431; Email: lienbruck@tauex.tau.ac.il

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

• Adults aged 18 years and older.
• Individuals living with overweight or obesity.
• Willingness and ability to comply with dietary recommendations and study procedures.
• Provision of written informed consent.

Exclusion Criteria

• Diagnosed metabolic or endocrine disorders known to affect energy expenditure.
• Use of medications known to substantially affect metabolism or body composition.
• Pregnancy or breastfeeding.
• Any medical condition that, in the opinion of the investigators, precludes safe participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Hypocaloric Dietary Intervention; Participants will follow individualized hypocaloric dietary plans designed to produce a moderate daily energy deficit based on measured resting metabolic rate. The intervention focuses on dietary energy restriction while supporting preservation of fat-free mass through adequate protein intake. Body composition and resting metabolic rate will be assessed before and after the intervention to evaluate metabolic responses to weight loss.

Behavioral: Hypocaloric Diet; Participants will follow individualized dietary plans designed to produce an energy deficit of approximately 500-600 kcal/day relative to measured resting metabolic rate. Protein intake will be prescribed at approximately 1.5 g/kg body weight per day to support preservation of fat-free mass. Dietary plans will be adjusted as needed during the intervention period, and participants will attend regular follow-up visits to monitor progress and adherence.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Resting Metabolic Rate	Change in resting metabolic rate (RMR) measured by indirect calorimetry between baseline and post-intervention assessment.	Baseline to end of dietary intervention (up to 12 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fat Mass	Change in total body fat mass measured using dual-energy X-ray absorptiometry (DXA).	Baseline to end of dietary intervention (up to 12 months)
Change in Fat-Free Mass	Change in total body fat-free mass measured using dual-energy X-ray absorptiometry (DXA).	Baseline to end of dietary intervention (up to 12 months)
Change in Body Weight	Change in body weight measured using a calibrated digital scale.	Baseline to end of dietary intervention (up to 12 months)
Change in Abdominal Circumference	Change in abdominal circumference measured using a standardized anthropometric tape at the midpoint between the lowest rib and iliac crest.	Baseline to end of dietary intervention (up to 12 months)
Intervention Duration	Total duration of participation in the hypocaloric dietary intervention, recorded in weeks from baseline to intervention completion.	Baseline to end of intervention (up to 12 months)
Physical Activity Modality	Self-reported type of physical activity performed during the intervention, categorized as aerobic, resistance, combined, or none.	Baseline to end of dietary intervention (up to 12 months)

Collaborators and Investigators

• Sponsor: Tel Aviv University
• Investigators: Principal Investigator: Yftach Gepner, PhD, Tel Aviv University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: May 31, 2026
• First Submitted That Met QC Criteria: May 31, 2026
• First Posted (Actual): June 4, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: May 31, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Energy expenditure; Weight loss; Body composition; Hypocaloric diet; Resting metabolic rate; Metabolic adaptation; Fat-free mass
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Body Weight Changes; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Weight Loss
• Other Study ID Numbers: 0012134-2

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