Energy Expenditure and Substrate Utilization During Acute Under- and Over-feeding

Study Overview
=================
Brief Summary
-----------------
This study will determine the impact of 24, 48 and 72 hours of over and underfeeding on energy expenditure as measured in the metabolic chamber at the UNC Chapel Hill Nutrition Research Institute (UNC NRI).

Detailed Description
-----------------
Subjects will complete a baseline eucaloric study day. Following this, subjects will be randomized to complete 3 days of overfeeding (150% of baseline eucaloric energy requirements) or 3 days of underfeeding (50% of baseline eucaloric energy requirements). After completing one of these study arms, subjects will cross-over and complete the second arm. All study arms will be separated by two weeks. 24-hour energy expenditure will be measured 3 times during each of 3 day periods. We hypothesize that the impact of over or underfeeding on EE will be evident after 24-hours and will be comparable to 72 hour EE.

Official Title
-----------------
Energy Expenditure and Substrate Utilization During Acute Under- and Over-feeding

Conditions
-----------------
Obesity

Intervention / Treatment
-----------------
* Other: 24-hour energy expenditure


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Woman Postmenopausal Aged 50-65 years BMI 25-35kg/m2 Not taking blood pressure or anti-inflammatory medications or any other medications that may impact the results Thyroid hormone profile within the normal reference range No medical condition which may impact the results (e.g. diabetes) Accustomed to eating regular meals including breakfast Exclusion Criteria: Smoker Heavy exerciser (defined as >150 minutes/week for more than 3 months) Abuses alcohol or drugs Vegetarian

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eucaloric Feeding<br>Subjects will complete an initial eucaloric feeding study day. During this study day, subjects will receive 100% of their calorie requirements. 24-hour energy expenditure will be measured. | Other: 24-hour energy expenditure<br>* To assess 24-hour energy expenditure and substrate utilization subjects will spend 23 hours and 15 minutes each day in the metabolic chamber at the UNC NRI. Subjects will be requested to arrive at the study center each morning following a 10hour overnight fast. During each study day, subjects remained sedentary. All meals were provided and were tailored to each subject's specific energy requirements and the study protocol (i.e. 50% or 150% of calorie requirements).<br>|
| Experimental: Underfeeding<br>Following the eucaloric feeding study day, subjects will undergo the underfeeding and overfeeding arms in random order. During the underfeeding study arm, subjects will receive 50% of their calorie requirements (as determined during the initial eucaloric study day) for 3 days. 24-hour energy expenditure will be measured. | Other: 24-hour energy expenditure<br>* To assess 24-hour energy expenditure and substrate utilization subjects will spend 23 hours and 15 minutes each day in the metabolic chamber at the UNC NRI. Subjects will be requested to arrive at the study center each morning following a 10hour overnight fast. During each study day, subjects remained sedentary. All meals were provided and were tailored to each subject's specific energy requirements and the study protocol (i.e. 50% or 150% of calorie requirements).<br>|
| Experimental: Overfeeding<br>Following the eucaloric feeding study day, subjects will undergo the underfeeding and overfeeding arms in random order. During the overfeeding study arm, subjects will receive 150% of their calorie requirements (as determined during the initial eucaloric study day) for 3 days. 24-hour energy expenditure will be measured. | Other: 24-hour energy expenditure<br>* To assess 24-hour energy expenditure and substrate utilization subjects will spend 23 hours and 15 minutes each day in the metabolic chamber at the UNC NRI. Subjects will be requested to arrive at the study center each morning following a 10hour overnight fast. During each study day, subjects remained sedentary. All meals were provided and were tailored to each subject's specific energy requirements and the study protocol (i.e. 50% or 150% of calorie requirements).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Energy Expenditure | 24-hour energy expenditure will be assessed using the metabolic chamber at UNC NRI. Energy expenditure will be measured during eucaloric feeding (subjects will receive 100% of calorie requirements), as well as during 24, 48 and 72 hours of under and overfeeding. | 24-hour energy expenditure will be assessed | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole blood transcriptomics | RNA will be extracted from whole blood. Transcriptomic profile will be assessed by microarray | Fasting a.m. sample, before lunch, and at 0.5, 2, and 4.5 hours post lunch | 
| Plasma metabolomics | Plasma metabolomic profile will be assessed using GC/MS and LC/MS platforms. | Fasting a.m. sample, before lunch, and at 0.5, 2, and 4.5 hours post lunch |