Testing the Adipose Expandability Hypothesis in Vivo During Overfeeding

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.


Eligibility Criteria:
Inclusion Criteria:

* Men and pre-menopausal women
* 18-42 years of age
* BMI 23-35 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 (± \~5% weight change)
* 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
* Chronic smokers or users of tobacco products who cannot abstain for the duration of the inpatient visits
* 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.