Experimental Overfeeding in Humans (ExpO)

Metabolic Changes in Response to Experimental Overfeeding: A Randomized Intervention Study

The objective of this study is to determine the homeostatic mechanisms that counteract weight gain in response to experimental overfeeding.

Study Overview

• Status: Completed
• Conditions: Obesity; Overfed
• Intervention / Treatment: Other: Isocaloric diet; Other: Overfeeding diet

Detailed Description

The homeostatic regulation of body weight implies that biological processes have evolved to protect energy stores from changes to the food environment. Accordingly, many individuals remain remarkably weight stable over years without carefully considering how much they eat or how much energy they expend, which has given rise to the theory that body weight is regulated around an individual biological 'set point'. Notably, overfeeding humans in experimentally controlled conditions, support this phenomenon, but the underlying mechanisms are unknown.

To systematically map out the components of the overfed state, the investigators will execute a 2-week randomized controlled overfeeding trial in lean and overweight individuals. The trial is preceded by a 1-week lead-in period and followed by a 2-wk controlled ad libitum study period. The comparison between lean and overweight subjects, men and women, enables the determination of whether a differential response in overfeeding-induced signals is present in relation to BMI and sex.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christoffer Clemmensen, Assoc. Prof.; Phone Number: +45 22 91 63 33; Email: chc@sund.ku.dk

Study Locations

• Denmark
  • Norrebro
    • Copenhagen, Norrebro, Denmark, 2200
      • University of Copenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 38 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female otherwise healthy subjects
• 20-40 years of age
• BMI (Body mass index) between 22-30 kg/m2

Exclusion Criteria:

• Present or previous cardiovascular disease, diabetes or thyroid-disease
• smoking
• more than 3 hours of planned physical activity per week

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group; Subjects in this group will have a daily energy intake equivalent of 100 % of their calculated normal daily energy intake.	Other: Isocaloric diet; Two weeks of isocaloric weight maintenance
Experimental: Overfed group; Subjects in this group will have a daily energy intake equivalent of 150 % of their calculated normal daily energy intake.	Other: Overfeeding diet; Two weeks of overfeeding

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in blood protein patterns using proteomics 1 week before, during 2 weeks of overfeeding and 2 weeks after overfeeding	Blood will be collected for proteomics at screening, at baseline, during the overfeeding intervention and during the 2-week ad libitum intervention. Samples will be measured using LCMS instrumentation consisting of a nanoelectrospray ion source to a Q Exactive HF mass spectrometer.	5 weeks
Changes in blood peptide patterns using peptidomics 1 week before, during 2 weeks of overfeeding and 2 weeks after overfeeding	Blood will be collected for peptidomics at screening, at baseline, during the overfeeding intervention and during the 2-week ad libitum intervention. Samples will be measured using LCMS instrumentation consisting of a nanoelectrospray ion source to a Q Exactive HF mass spectrometer.	5 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body weight	Body weight will be measured (in kilograms) daily during the intervention using electronic Fitbit Aria 2 weight scale.	5 weeks
Fat biopsy from subcutaneous adipose tissue before and after 2 weeks of overfeeding	Fat biopsies are obtained using Bergström biopsy needle from subcutaneous adipose tissue in the abdominal region before and after 14 days of overfeeding to assess regulated enzymes and proteins.	2 weeks
Microdialysate from subcutaneous adipose tissue before and after 2 weeks of overfeeding. The samples will be used for detection of known and unknown secreted factors	Microdialysates are collected from micro dialysis catheters inserted into the subcutaneous adipose tissue in the abdominal region before and after 14 days of overfeeding to assess regulated enzymes and proteins.	2 weeks
Body composition in 40 subjects before and after overfeeding	Body composition will be measured using Dual-Energy X-ray Absorptiometry (DXA) at screening (1 week before baseline), at baseline and after 14 days of overfeeding. The DXA scan enables the detection of body lean mass and body fat mass in kg.	3 weeks
Mixed meal test	Before and after the intervention a mixed meal test will be performed	2 weeks
Changes in blood metabolome 1 week before, during 2 weeks of overfeeding and 2 weeks after overfeeding	Blood will be collected for metabolomics at screening, at baseline, during the overfeeding intervention and during the 2-week ad libitum intervention. Metabolomics will be performed using Mass Spectrometry.	5 weeks
Activity profile of 40 subjects during the 5 week study period	Assessment of daily physical activity levels (wearables and doubly-labelled water)	5 weeks
Detection of circulating factors	The investigators will measure the concentration of known circulating factors from fasted blood samples and from blood samples obtained during mixed meal test, such as: Glucose, insulin, hsCRP, Hba1c, cortisol, ACTH, lactate, fatty acids, triglycerides, glycerol, catecholamines, leptin, ghrelin, adiponectin, glucagon, GDF15, FGF21, FGF19, GIP, GLP-1, PYY, CCK, interleukins, cytokines, tissue-kines, T3, T4, TSH, cholesterol.	5 weeks
Gut microbiome profile before and after 14 days of overfeeding	Feces samples will be collected before and after 14 days of overfeeding and microbiome composition will be analyzed by using UPLC-MS/GC-MS.	2 weeks

Collaborators and Investigators

• Sponsor: University of Copenhagen
• Investigators: Principal Investigator: Christoffer Clemmensen, Assoc. Prof., Assoc. prof. NNF Center for Basic Metabolic Research

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2019
• Primary Completion (Actual): January 1, 2023
• Study Completion (Actual): January 1, 2023

Study Registration Dates

• First Submitted: August 8, 2019
• First Submitted That Met QC Criteria: August 20, 2019
• First Posted (Actual): August 22, 2019

Study Record Updates

• Last Update Posted (Actual): May 9, 2023
• Last Update Submitted That Met QC Criteria: May 8, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: ExpO

Drug and device information, study documents

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