EAT 2: Testing the Adipose Expandability Hypothesis In Vivo During Overfeeding

Sponsor

Pennington Biomedical Research Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04583514

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Enrollment

Location

Arms

51.5

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Adipose, or fat, tissue is a plastic organ that retains the ability to expand and store excess calories during positive energy balance in humans. The capacity of subcutaneous (subQ) adipose tissue to expand and remodel is an important determinant of obesity-related health complications, and impaired expansion of subQ fat tissue is thought to contribute to the risk of diseases such as the Metabolic Syndrome (MetS) and type 2 diabetes mellitus (T2D). The objectives of the study are to evaluate the changes and mechanisms of (subQ) adipose tissue expandability that occur as a result of short-term weight gain and to investigate the effects on cardio-metabolic health outcomes. Findings from this study will provide new insight into the dynamics of adipose expansion and remodeling during changes in energy balance and how this may impact future fat tissue function and metabolic health.

Condition or Disease	Intervention/Treatment	Phase
Overweight and Obesity Metabolic Syndrome	Behavioral: Control Behavioral: Overfeeding	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Investigator, Outcomes Assessor)

Primary Purpose:

Other

Official Title:

Testing the Adipose Expandability Hypothesis In Vivo During Overfeeding

Actual Study Start Date :

Sep 15, 2020

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Control The control group will be expected to maintain their weight within 1 kg of baseline weight throughout the duration of the study.	Behavioral: Control Weight-stable Control group
Experimental: Overfeeding The overfeeding group will be subjected to a similar relative change in energy intake, in which their dietary intake will be 30% more kcal/d than needed for weight maintenance.	Behavioral: Overfeeding 30% Overfeeding group

Arm

Intervention/Treatment

Experimental: Control

The control group will be expected to maintain their weight within 1 kg of baseline weight throughout the duration of the study.

Behavioral: Control

Weight-stable Control group

Experimental: Overfeeding

The overfeeding group will be subjected to a similar relative change in energy intake, in which their dietary intake will be 30% more kcal/d than needed for weight maintenance.

Behavioral: Overfeeding

30% Overfeeding group

Outcome Measures

Primary Outcome Measures

Adipose tissue expansion and remodeling -- in vivo adipocyte formation [8 weeks]
Following the consumption of deuterium-labeled water (2H2O; heavy water), adipose tissue biopsies from the subcutaneous abdominal and femoral depots will be collected. The 2H from the heavy water is enriched into the DNA of newly synthesized cells. The primary outcome is to assess changes in new adipocyte formation in vivo and other mechanisms of adipose expansion and remodeling in response to 30% overfeeding (OF group) relative to the weight-stable CTL group.

Secondary Outcome Measures

Adipose tissue expansion and remodeling -- in vivo triglyceride synthesis [8 weeks]
Following the consumption of deuterium-labeled water (2H2O; heavy water), adipose tissue biopsies from the subcutaneous abdominal and femoral depots will be collected. The 2H from the heavy water is incorporated into the glycerol component of the adipose, providing a measure of new triglyceride synthesis. A secondary outcome is to assess changes in triglyceride synthesis in vivo and other mechanisms of adipose expansion and remodeling in response to 30% overfeeding (OF group) relative to the weight-stable CTL group.
Cardiometabolic health outcomes [8 weeks]
A secondary outcome is to investigate the correlation between mechanisms of adipose tissue expansion and remodeling with changes in metabolic health outcomes (i.e. abdominal adiposity; insulin sensitivity; ectopic lipid) in response to 30% OF relative to the CTL group.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 42 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Men and pre-menopausal women
18-42 years of age
BMI 25-30 kg/m2 (± 0.5 will be accepted)
Are willing to drink deuterium-labeled water (2H2O) for 8 weeks
Are willing to be randomized to either a CTL or 30% OF group
For women, if not using pharmaceutical (hormonal) contraception (i.e. birth control pills, vaginal ring, injections, or implant), must agree to use either a double barrier method as a form of birth control to prevent pregnancy (i.e. male condom with spermicide, with or without cervical cap or diaphragm); use implants or intrauterine contraceptive devices; have a tubal ligation (surgically sterile); practice abstinence; or be in an established relationship with a vasectomized or same sex partner during the entire duration of the study
Must be willing to adhere to all study procedures, including attendance at all study visits
If enrolled, agree to maintain the same level of physical activity throughout the duration of the study
Must be willing to have blood stored for future research

Exclusion Criteria:

Unstable weight in the last 3 months (± ~7 lbs)
Diagnosis of Type 1 or 2 diabetes or a fasting blood glucose > 110 mg/dL
Average screening blood pressure > 140/90 mmHg
Diagnosis of major organ disease (e.g. heart, kidney, lung, thyroid, liver disease) or abnormal liver enzymes that are, in the opinion of the MI, clinically significant and represent a problem for study inclusion.
Self-reported positive test for human immunodeficiency virus, hepatitis B or hepatitis C
Any current or previous eating disorders
Chronic use of systemic glucocorticoids (steroids), systemic adrenergic-stimulating agents, beta-blockers, antipsychotic medications, thiazolidinediones and other medications that may cause clinically significant weight gain or loss)
Chronic use of prescription weight loss medications or over the counter weight loss medications which, in the opinion of the MI, will impact the study
Chronic use of anti-depressant medications for less than 3 months
Smoking or use of tobacco products in the last 3 months
Previous bariatric or other surgeries for obesity
Had cancer in the last 5 years (some skin cancers acceptable)
Pregnancy, breastfeeding, or planned pregnancy for the upcoming 6 months
Partial or full hysterectomy
PCOS
Diagnosed psychotic conditions.