BATokines as Biomarkers of Brown Fat in Humans

Summary

Brown adipose tissue (BAT) burns excess calories to produce heat in response to environmental cold. Rapidly growing evidence from rodent and human studies suggests that the presence and activation of brown fat are far more beneficial for whole body metabolism and cardiometabolic health than previously appreciated. Despite the clear associations between brown fat and metabolic health, we lack both: cost-effective means of detecting brown fat in humans as well as comprehensive insights into how brown fat facilitates metabolism on a molecular level in humans.

Emerging evidence suggests that the benefits of brown fat activation are mediated, at least in part, by secretion of specific molecules into the bloodstream which signal to metabolically active organs such as skeletal muscle, liver and brain. A number of these so-called brown adipokines (or BATokines) have now been discovered in mice and shown to positively impact glucose homeostasis, liver and muscle function. Human deep-neck brown fat biopsies reveal that \>1000 molecules could potentially be secreted from brown fat, and \>400 are released by human brown fat cells in a dish, representing a major opportunity for discovery of high translational value.

Here, we aim to identify a screen of first potential blood biomarkers of brown fat in healthy young humans. This will be achieved by analyzing plasma proteins in subjects with 'inactive brown fat' (warm) and 'activated brown fat' (3-hr cold exposure, cooling vests) using high-throughput technologies (SOMAscan and O-link) to identify temperature-sensitive brown fat-enriched molecules. This preliminary data will guide a larger follow up study in which we envision studying lean and obese (insulin sensitive and insulin resistant) subjects of various age groups and race/ethnicity. Human BATokines identified here will become primary targets for manipulation in experimental animals to assess their therapeutic potential against obesity, T2D, and associated diseases. Additionally, since current methods of brown fat detection in human rely on deep neck biopsies or costly 18-FDG-PET/CT scans, identification of blood biomarkers of brown fat would offer a cost-effective and non-invasive alternative for prediction of metabolic health in humans.

Conditions

• Healthy Lifestyle

Interventions

OTHER

Cooling Vest Procedure

A cold vest will be placed on the participant (consisting of a water-perfused CFA wearable vest, size S-M or M-L with adjustable straps Polar Products, Stow, OH; attached to a small 'cooler' reservoir to circulate cold water between the vest and the cooler; Product link: https://www.polarproducts.com/polarshop/pc/CoolOR-13-Quart-System-with-Arctic-Chiller-p24757.htm This product is safe and recommended by experimental guidelines and BARCIST criteria for human BAT studies. Note, the cooling vest will be cleaned between participants according to the manufacturer's guidelines found here: https://www.polarproducts.com/polarshop/pc/catalog/pdf/Polar\_CoolFlow\_Manual.pdf. Briefly, the vest will be hand washed with a mild detergent and warm soapy water and air-dried. The vest will then be stored in a clean, dry environment with ventilation.

OTHER

Fasting overnight

Participants will be requested to refrain from food and caloric drinks overnight (starting at 10pm) prior to the hospital visit. Blood will then be drawn the following morning (between 8 and 9am) and 3hrs later (between 11am and noon). Participants will be sat in a room with ambient temperature (room temperature w/o cooling) between the two blood draws.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center

  collaborator OTHER

• Rockefeller University

  lead OTHER

Principal Investigators

• Kaja Plucinska, PhD · The Rockefeller University

• Paul Cohen, PhD · The Rockefeller University

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

28 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2021-10-12

Primary Completion

2026-12-31

Completion

2026-12-31

Countries

• United States

Study Locations