The Role of Brown Adipose Tissue in Triglyceride Clearance in People

Summary

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.

Conditions

• Obesity

Interventions

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).

Sponsors & Collaborators

• Washington University School of Medicine

  lead OTHER

Principal Investigators

• Maria Chondronikola, PhD, RDN · University of California, Davis

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

21 Years

Max Age

65 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2016-05-31

Primary Completion

2019-06-30

Completion

2019-06-30

Countries

• United States

Study Locations