The Role of Brown Adipose Tissue in Triglyceride Clearance in People



Status:Recruiting
Conditions:Obesity Weight Loss
Therapuetic Areas:Endocrinology
Healthy:No
Age Range:21 - 65
Updated:1/6/2019
Start Date:May 2016
End Date:August 2020
Contact:Maria Chondronikola, PhD, RDN
Email:mchondr@wustl.edu
Phone:314-3622016

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The recent discovery of functional brown adipose tissue (BAT) in humans has led to a paradigm
shift in adipose tissue biology; it is now believed that adipocytes may play a significant
role in regulating substrate metabolism. Given that the resurgence in the interest in human
BAT is still in its infancy, a number of fundamental questions pertaining to the role of BAT
in human physiology remain unanswered. One area of particular importance, but poorly
understood, is the potential effect of BAT on triglyceride (TG) metabolism. Data from a
series of studies have found that BAT is inversely associated with adiposity, high blood
lipids, and fatty liver in people. However, the role of BAT in the regulation of TG
metabolism in people is not known. The overall goal of this study is to determine the
physiological importance of the human BAT in TG metabolism. To this end, we are planning to
study forty overweight/obese women with high amounts of BAT (BAT+, n=20) and with no/minimal
BAT (BAT-, n=20) both under thermoneutrality and mild cold exposure (~2 weeks apart). The
investigators hypothesize that BAT+ subjects will demonstrate greater plasma very low density
lipoprotein-triglycerides (VLDL-TG) clearance rate during cold exposure compared to BAT-
subjects and upregulation of genes and proteins involved in lipid metabolism only in BAT (but
not muscle and white adipose tissue). Infusion of stable isotope tracers and metabolic
modeling techniques will be used to assess VLDL-TG kinetics. Positron emission tomography
computed tomography will be used for the identification and quantification of BAT.
Supraclavicular BAT, abdominal white adipose tissue, and skeletal muscle tissue biopsies
during cold exposure and thermoneutral conditions in conjunction with molecular biology
techniques will used to measure expression of genes and proteins involved in lipid
metabolism.


Inclusion Criteria:

- Age ≥ 21 and ≤ 65 years

- BMI 25.0-35.0 kg/m2

Exclusion Criteria:

- Men

- Previous bariatric surgery or gastrointestinal surgery

- Structured exercise > 2 days/week for ≥ 35 min of intense exercise (e.g., jogging,
activity that causes heavy breathing and sweating) or ≥ 150 min per week of moderate
intensity exercise (e.g., brisk walking)

- Unstable weight (> 5% change during the last 2 months before entering the study)

- Significant organ system dysfunction (e.g., diabetes requiring medications, severe
pulmonary, disorders of the gastrointestinal tract, kidney or cardiovascular disease)

- Current cancer or cancer that has been in remission for < 5 years

- Conditions that render subject unable to complete all testing procedures (e.g., severe
ambulatory impairments, limb amputations, or metal implants that interfere with
imaging procedures; coagulation disorders)

- Use of medications that are judged by the investigators to affect the study outcome
measures or increase the risk of study procedures (e.g., anticoagulants) and that
cannot be temporarily discontinued for this study

- Smoke cigarettes or use of illegal drugs

- Consumption of >14 units of alcohol (e.g., glass of wine or bottle of beer) per week

- Pregnant or lactating

- Persons who are not able to grant voluntary informed consent

- Persons who are unable or unwilling to follow the study protocol or who, for any
reason, the research team considers not an appropriate candidate for this study,
including non-compliance with screening appointments or study visits
We found this trial at
1
site
660 S Euclid Ave
Saint Louis, Missouri 63110
(314) 362-5000
Principal Investigator: Samuel Klein, MD
Phone: 314-362-2016
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
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