Establishment of the 2H-labeling Protocol at Pennington Biomedical Research Center

Establishment of the 2H-labeling Protocol to Assess in Vivo Adipose Tissue Dynamics at PBRC

A method has been developed to measure in vivo adipose kinetics and turnover rates, which is a substantive departure from previous indirect and in vitro approaches. This technique involves drinking deuterium (2H)-labeled water, with an initial ramp-up to increase body water 2H enrichment, followed by daily intake to maintain enrichment values. The 2H from the heavy water is incorporated into the DNA of the dividing cells, as well as the lipid component, providing measures of cell formation, lipid synthesis, and adipose turnover. The objective of the proposed study is to enroll women who are overweight (sedentary or physically active) in order to collect 2H-enriched adipose tissue specimens that will be utilized to establish this innovative 2H-labeling protocol at Pennington Biomedical Research Center. This study will also assess adipose kinetics in individuals with different levels of physical activity to better understand the association between in vivo adipose cell kinetics, physical activity, and metabolic health in humans.

Inclusion Criteria:

• Pre-menopausal women
• 18-40 years of age
• BMI 25-29.9 kg/m2 (+/- 0.5 will be accepted)
• Are willing to drink deuterium-labeled water (2H2O) for 6 weeks
• Must be willing to comply with all study procedures, including adipose biopsies and a DXA scan
• If applicable, hormonal contraception must have been started at least 2 months before entering the study. If enrolled, subject must also agree to not alter hormonal birth control method, dose, or regimen throughout the duration of the study
• If not using pharmaceutical (hormonal) contraception (i.e. birth control pills, vaginal ring, injections, or implant), agree to use a double barrier method as a form of birth control to prevent pregnancy
• Must be classified as either sedentary (achieve < 75 minutes of moderate-intensity or < 37 minutes of vigorous-intensity aerobic physical activity per week) or very physically active (achieve > 225 minutes of moderate-intensity or > 112 minutes of vigorous-intensity aerobic physical activity per week). Simple questions to assess physical activity level will be administered during the phone screening as well as the clinic screening visit.
• If enrolled, agree to not alter dose, level, or regimen of physical activity throughout the duration of the study

Exclusion Criteria:

• Unstable weight in the last 3 months (gain or loss >7 lb (3.2 kg)
• Significant changes in the diet or level of physical activity within the past month
• History of clinically diagnosed diabetes or a fasting blood glucose > 110 mg/dL
• An average screening blood pressure >140/90
• Have major organ disease (i.e. heart, kidney, lung, thyroid, or liver) or abnormal liver enzymes that are, in the opinion of the medical investigator, clinically significant and represent a problem for study inclusion.
• Self-reported positive test for human immunodeficiency virus, hepatitis B and hepatitis C
• Chronic use of systemic glucocorticoids, systemic adrenergic-stimulating agents, anti-psychotic/anti-depressant medications, thiazolidinediones and other medications that may cause clinically significant weight gain or loss
• Chronic use of prescription or over-the-counter weight loss medications which, in the opinion of the MI, will impact the study.
• Smoking or use of tobacco products in the last 3 months
• Pregnancy, breastfeeding, or planned pregnancy for the upcoming 2 months
• Previous bariatric or other surgeries for obesity
• Diagnosed psychotic conditions