Experimental Approach to Test Predictions of Body Weight Regulation Models (DIP)

The regulation of human body weight and fatness is not fully understood. Although some models of regulation have been proposed (set point, dual-intervention point, others), no studies have been designed to test their predictions. In this pilot and feasibility study, the investigators will implement an experimental approach to test the predictions of models of body weight regulation in humans. Men and women with either low body weight or obesity will be exposed to a 2-day fasting followed by a 2-day ad-libitum refeeding. During the entire fasting-refeeding period, energy intake and expenditure will be accurately measured within metabolic chambers. The investigators will therefore determine the compensatory responses to fasting elicited to prevent weight loss. The results will serve to design and power future studies to better understand body weight regulation.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Underweight
• Intervention / Treatment: Behavioral: Fasting-refeeding cycle

Detailed Description

Background:

Although body weight regulation models have been proposed, experimental approaches for testing their predictions are lacking. The set point (SP) model proposes that a biologically determined fatness is defended by activating compensatory responses to prevent its change. The dual-intervention point (DIP) model proposes that there are two levels of fatness (lower and upper intervention points) within which fatness is weakly regulated. Compensatory responses would only be activated once the lower or upper intervention points are reached. In response to prolonged fasting, the SP model predicts the compensatory responses to be independent of the initial body weight. In contrast, the DIP model predicts higher responses in individuals who are closer to the lower intervention point (low body weight) compared to those who are farther away (obesity). None of these models predicts a different response in men vs. women. Our pilot and feasibility study will implement an experimental approach to test these predictions in humans by thoroughly measuring compensatory responses in energy expenditure and energy intake.

Design:

Twelve individuals (3 men with low body weight and 3 with obesity; 3 women with low body weight and 3 with obesity) will be kept inpatient in metabolic chambers for 5 consecutive days and exposed to a 1-day energy balance, 2-day fasting, and 2-day ad-libitum refeeding. The primary outcome will be the extent of compensatory response, calculated as the cumulative energy balance during the 5-day inpatient period.

Objectives:

1. To determine the extent of compensatory response induced by a 2-day fasting followed by a 2-day ad-libitum refeeding in humans overall and among different subgroups (low body weight, obesity, men, women).
2. To explore the timing of the compensatory responses during a 2-day fasting followed by a 2-day ad-libitum refeeding in humans.
3. To explore potential physiological determinants of the inter-individual variability in the compensatory response induced by a 2-day fasting followed by a 2-day ad-libitum refeeding in humans.

Relevance:

Understanding how body weight is regulated in humans can help to prevent or treat obesity. In this pilot and feasibility study, the investigators propose an experimental approach to test the predictions of two body weight regulation models in response to fasting and explore potential sex differences. These preliminary data will be used to design and power future studies for testing models of body weight regulation in humans.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eric Ravussin, PhD; Phone Number: 2257633186; Email: Eric.Ravussin@pbrc.edu
• Study Contact Backup: Name: Rodrigo Fernandez-Verdejo, PhD; Phone Number: 2257632594; Email: Rodrigo.Fernandez@pbrc.edu

Study Locations

• United States
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Recruiting
      • Pennington Biomedical Research Center
      • Contact: Rodrigo Fernández-Verdejo, PhD; Phone Number: 225-763-2594; Email: rodrigo.fernandez@pbrc.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Body mass index lower than 20 kg/m2 for the low body weight group, or 30 kg/m2 or greater for the obesity group
• 18-40 years old
• Nulliparous and regular menstrual cycle (25-35 days) during the last six months (in women)
• Normal thyroid function, blood count, and chemistry 15 panel (normal plasma glucose will be considered at <100 mg/dL; normal serum HDL cholesterol at >=50 mg/dL for women and >=40 mg/dL for men; and normal serum triglycerides at <150 mg/dL).
• Self-reported weight stability during the last six months (±3 kg)
• Rate the liking of at least one of the flavored liquid meals (Ensure Plus, Abbot Nutrition) between 5 and 8 on a 9-point Likert scale
• Willing to only drink up to two assigned flavors of Ensure Plus for two consecutive days

Exclusion Criteria:

• Eating disorders as indicated by a global score ≥2.80 in the Eating Disorder Examination Questionnaire, or a previous diagnosis of an eating disorder
• For the low body weight group, having food insecurity (with or without hunger) as assessed by the USDA
• Recreational moderate-intensity physical activity ≥150 min/week, recreational vigorous-intensity physical activity ≥75 min/week, or a combination of recreational moderate-intensity and vigorous-intensity physical activity (moderate time + [2 × vigorous time]) ≥150 min/week as assessed by the Global Physical Activity Questionnaire, or being a professional athlete
• Cigarette or vape smoking
• Intake of more than 14 alcoholic drinks per week
• Use of medications that may affect energy intake and/or expenditure, for example, semaglutide, liraglutide, exenatide, other GLP-1 receptor agonists, phentermine-topiramate, naltrexone-bupropion, orlistat, metformin, SGLT2 inhibitors, pramlintide, levocarnitine, amphetamines, and amphetamine-like drugs
• Human immunodeficiency virus, galactosemia, and lactose intolerance
• Diseases that affect energy homeostasis including endocrine such as hypo/hyperthyroidism, or type 1 or 2 diabetes; cancer; chronic pulmonary diseases; cardiovascular disease; and renal disease
• History of inflammatory bowel disease (ulcerative colitis, Crohn's), malabsorption syndromes (intestinal, pancreatic), and sprue or gluten intolerance
• Having moderate to severe sleep apnea defined as an oxygen desaturation index >10 times/hour assessed by overnight oximetry to be conducted on the night following the screening visit
• Use of oral hormonal contraceptives or less than 6 months using a hormonal intrauterine device (in women)
• Adults who are unable to consent
• Prisoners
• Currently pregnant or breastfeeding (in women)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• 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: Fasting-refeeding cycle; Participants will be maintained in metabolic chambers and exposed to 1 day of energy balance, 2 days of fasting, and 2 days of ad-libitum refeeding.	Behavioral: Fasting-refeeding cycle; Participants will be maintained in metabolic chambers and exposed to 1 day of energy balance with a standard diet, 2 days of fasting (only water), and 2 days of ad-libitum refeeding using a liquid diet provided in hydration bladders to avoid portion control.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compensatory response	Cumulative energy balance during the fasting-refeeding cycle	The cumulative energy balance is calculated one time using the data of 5 inpatient days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Timing of the compensatory response	Cumulative energy balance during different time periods of the 5-day fasting-refeeding cycle	The cumulative energy balance calculated for the following time periods along the 5-day fasting-refeeding cycle: day 1 to 2, day 1 to 3, day 1 to 4, during fasting (day 2 to 3), and during refeeding (day 4 to 5)
Protein balance	Protein balance (intake minus oxidation) during the fasting-refeeding cycle	Protein balance is calculated one time using the data of 5 inpatient days
Carbohydrate balance	Carbohydrate balance (intake minus oxidation) during the fasting-refeeding cycle	Carbohydrate balance is calculated one time using the data of 5 inpatient days
Lipid balance	Lipid balance (intake minus oxidation) during the fasting-refeeding cycle	Lipid balance is calculated one time using the data of 5 inpatient days
Overall appetite	Calculated from the results of visual analog scales that record hunger, satiety, fullness, and prospective food consumption	Overall appetite is measured 8 times per day (every 2 hours from approximately 8:00 AM) during the 5 inpatient days
Food preference	Measured using the Food Preference Questionnaire	Measured once a day, in the fasting state (at approximately 8:00 AM), during the 5 inpatient days
Physical activity	Measured with wrist-worn accelerometers	Measured continuously (i.e. for 24 hours) every day during the 5 inpatient days
Sleeping metabolic rate	Measured within the metabolic chamber, between 2:00 and 5:00 AM, and extrapolated to 24 hours	Measured every day during the 5 inpatient days
Leptin	Circulating concentrations of leptin	Measured once a day, in the fasting state (at approximately 8:00 AM), during the 5 inpatient days
Metabolites	Circulating concentrations of glucose, fatty acids, ketone bodies	Measured once a day, in the fasting state (at approximately 8:00 AM), during the 5 inpatient days
Appetite-regulating hormones	Circulating concentrations of ghrelin and insulin	Measured once a day, in the fasting state (at approximately 8:00 AM), during the 5 inpatient days
Thyroid axis	Circulating concentrations of T4	Measured once a day, in the fasting state (at approximately 8:00 AM), during the 5 inpatient days

Collaborators and Investigators

• Sponsor: Pennington Biomedical Research Center
• Collaborators: Tulane University
• Investigators: Principal Investigator: Rodrigo Fernandez-Verdejo, PhD, Pennington Biomedical Research Center; Principal Investigator: Eric Ravussin, PhD, Pennington Biomedical Research Center; Principal Investigator: Dragana Lovre, MD, Tulane University

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 3, 2026

Study Registration Dates

• First Submitted: March 1, 2024
• First Submitted That Met QC Criteria: March 7, 2024
• First Posted (Actual): March 13, 2024

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Energy expenditure; Energy balance; Energy intake; Set point model; Dual-intervention point model
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Thinness
• Other Study ID Numbers: PBRC 2023-069

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified data collected will be shared upon appropriate request as part of the NORC repository of Pennington Biomedical Research Center
• IPD Sharing Time Frame: After publication of the results for the main outcome
• IPD Sharing Access Criteria: Upon appropriate request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No