Obesity
Conditions
Keywords
Adipose tissue, epigenetic, abdominal gluteal fat
Brief summary
The purpose of this study is to collect data to help researchers better understand the different ways that women or men store fat (apple shape versus pear shape).
Interventions
A DEXA scan for body composition will also be completed. After a MRI safety screening a whole body MRI for the volumetric measurement of visceral fat, subcutaneous fat, liver, kidneys, heart, brain, skeletal muscle and intramuscular adipose tissue (IMAT) and hepatic lipid by MRS will be performed. Whole body imaging will include low resolution positioning images, followed by several sets of 3D images which will be digitally connected to create a 3D image the entire length of the body. The liver spectroscopy will be performed using PRESS (point resolved spectroscopy) and STEAM (Stimulated Echo Acquisition Mode) sequence during the same imaging session, using the whole body images for positioning.
Two biopsies will be performed to collect fat tissue from the abdomen and thigh region.
Insertion of two intravenous (IV) catheters for performing a Frequently Sampled Intravenous Glucose Tolerance Test (FSIGTT) to measure the acute insulin response to glucose (AIRg) and insulin sensitivity (Si) will be performed. Resting metabolic rate (RMR) will be used to measure metabolic flexibility. Point of care blood glucose measurements will be taken frequently to ensure safety.
Sponsors
Study design
Eligibility
Inclusion criteria
* Age 18-45 years inclusive; * BMI 23-35 kg/m2 inclusive; * HbA1C \<6.0%; * Weight stable (± 3 kg) during the 3 months prior to enrollment; * Women must be \> 9 months post-partum; * Able to provide written, informed consent.
Exclusion criteria
* Postmenopausal women * Women with an oophorectomy * Fasting plasma glucose \> 126 mg/dL, or diagnosis with Type 2 Diabetes (T2DM) * Untreated or symptomatic thyroid disease. * Aminotransferase or aspartate aminotransferase \> 3x upper limit of laboratory reference range, or known diagnosis of liver disease. * Creatinine \> 2x upper limit of laboratory reference range, or known diagnosis of kidney disease. * Uncontrolled hypertension (BP \> 140 systolic or \> 90 diastolic) * New onset (\<3 months on a stable regime) use of oral contraceptives or hormone replacement therapy. * History of drug or alcohol abuse (\> 3 drinks per day) within the last 5 years, or psychiatric disease prohibiting adherence to study protocol. Current drug use may be determine by plasma or urine drug screens. * History of cancer within the last 5 years (skin cancers, with the exception of melanoma, may be acceptable). * History of organ transplant. * Myocardial Infarction within the last 6 months. * Current treatment with blood thinners or antiplatelet medications that cannot be safely stopped for biopsy and testing procedures. * History of HIV, active Hepatitis B or C or tuberculosis * Presence of clinically significant abnormalities on EKG. * Current smokers (smoking within the past 3 months). * Use of any medications known to influence glucose, fat and/or energy metabolism within the last 3 months (eg. growth hormone therapy, glucocorticoids \[steroids\], etc.) * Other chronic or acute illness that might affect study results / interpretation in the opinion of the clinical * Other items related to procedural risk (outlined below) such as bleeding disorder, claustrophobia, etc. * Elevated high sensitivity c-reactive protein or known active infection. * There are some implants which are MR compatible (safe) but would cause artifacts which could obscure our ability to measure an organ, e.g. full braces may negate the ability to measure brain size.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Epigenetic marks in abdominal vs gluteal subcutaneous adipose tissue and adipocytes | 6 weeks | The preadipocytes obtained from biopsies of Abdominal Fat and Gluteofemoral Fat from patients in the 'pears' woman, 'apple' women and men will be cultured by our standard methods in proliferative medium followed by our standard protocol for differentiation into mature adipocytes. We propose to evaluate samples from 3 individuals from each Group to identify a large number of differentially regulated regions genome wide. All the data obtained in vitro in culture cells will be compared with the data obtained from RNA and chromatin isolated from the whole tissue Abdominal fat and Gluteofemoral fat biopsies |
Countries
United States
Contacts
Study Principal Investigator