The Role of Brown Adipose Tissue in Triglyceride Clearance in People (BAT-TG)

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 overweight/obese women with high amounts of BAT (BAT+, n=14) and with no/minimal BAT (BAT-, n=14) both under thermoneutrality and mild cold exposure (~2 weeks apart). The investigators hypothesize that BAT+ participants will demonstrate greater plasma very low-density lipoprotein triglycerides (VLDL-TG) clearance rate compared to BAT- participants, and higher expression of genes 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 involved in lipid metabolism.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Other: Cold exposure; Other: Exposure to thermoneutral conditions

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: BAT+; Individuals with significant amounts of BAT (>20 ml)	Other: Cold exposure; During cold exposure intervention, we will use an individualized cold exposure protocol above the individual shivering threshold of each participant using liquid condition garments and a temperature controlled room.; Other: Exposure to thermoneutral conditions; For the thermoneutral conditions intervention, subjects will be exposed to thermoneutral conditions (~26-28°C).
Other: BAT-; Individuals with no/minimal amounts of BAT (<20 ml)	Other: Cold exposure; During cold exposure intervention, we will use an individualized cold exposure protocol above the individual shivering threshold of each participant using liquid condition garments and a temperature controlled room.; Other: Exposure to thermoneutral conditions; For the thermoneutral conditions intervention, subjects will be exposed to thermoneutral conditions (~26-28°C).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of VLDL-TG clearance	The rate of VLDL-TG clearance from plasma will be assessed using infusion of stable isotopes.	12 hours

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Maria Chondronikola, PhD, RDN, University of California, Davis

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: May 20, 2016
• First Submitted That Met QC Criteria: May 25, 2016
• First Posted (Estimate): May 30, 2016

Study Record Updates

• Last Update Posted (Actual): March 15, 2022
• Last Update Submitted That Met QC Criteria: March 14, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 201602059

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No