BATokines as Biomarkers of Brown Fat in Humans

NCT05050240 | Active Not Recruiting

• 1 other identifier: KPL-1023
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

metabolism; cold exposure; brown fat; blood biomarkers

Outcome Measures

Primary Outcomes (1)

• Identification of cold-regulated blood proteome

  Mass spectrometry generates a list of proteins for each sample. We will compare fold of change before and after cooling - a true change is defined as 1.5-fold.

  Before and after a 3 hour cooling procedure

Secondary Outcomes (4)

• Changes in HbA1c post cooling procedure using absorbance assay

  Before and after a 3 hour cooling procedure

• Changes in insulin post cooling procedure using enzyme-linked immunosorbent assay (ELISA)

  Before and after a 3 hour cooling procedure

• Changes in triglycerides post cooling procedure using absorbance assay

  Before and after a 3 hour cooling procedure

• Changes in TSH post cooling procedure using absorbance assay

  Before and after a 3 hour cooling procedure

Study Arms (2)

Cold Exposure

EXPERIMENTAL

The cold vest procedure: The first blood draw will be taken from participants before the cooling procedure (time 0, 30mL blood). Participants will then be requested to put on hospital scrubs and the cooling vest will be placed on them. Since muscle shivering is an alternative way of heat production (skeletal thermogenesis), we will first determine individual 'shivering threshold' for each participant (coldest tolerable temperature; typically 14°C / 57.2F), based on participant-report and direct observation. The cold vest will then be kept on for 3 hours with a temp set to the coldest tolerable temperature (shivering threshold +2°C (\~16-17°C / 60.8F-62.6F) and body temperature will be monitored by a tympanic thermometer. Following 3 hours, 30mL of blood will be drawn (Time 180min). All participants will be re-warmed with blankets after cooling has been completed, and offered a warm drink and a snack.

Other: Cooling Vest Procedure

Fasted procedure without cooling

ACTIVE COMPARATOR

This arm has been added in order to exclude the effects of prolonged fasting on blood analytes. Previously enrolled participants will be re-invited to donate blood after 12hr fast and 3hrs later (15hr fast) without the cooling procedure. Participants will be re-consented for this lab appointment. The night prior the visit, the participants will be instructed to fast from 10:00pm. At the time of visit vital signs and anthropomorphic measurements will be taken. Blood Draw: The first blood draw will take place in the morning. Participant will then be asked to sit in the procedure room for 3 hours at room temperature; second blood draw will take place after 3 hrs. Total of 38ml of blood will be drawn. Blood will be used for clinical labs (fasting glucose, Hba1c, TSH, TG) and research.

Other: Fasting overnight

Interventions

Cooling Vest Procedure OTHER

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.

Cold Exposure

Fasting overnight OTHER

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.

Fasted procedure without cooling

Eligibility Criteria

• Age: 18 Years - 28 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age between 18 and 28
• BMI \>19 and \< 25

You may not qualify if:

• Diabetes type I or II (self-report)
• Diagnosis of thyroid disease (including goiter, hyperthyroidism, hypothyroidism, thyroiditis) (self-report)
• Diagnosis with cancer including skin cancer (self-report)
• Diagnosis or evidence of Raynaud's Syndrome or systemic sclerosis (self report)
• Previously or currently diagnosed with SARS-Cov-2 infection/COVID-19 (secondary to unknown immune responses)
• Any vaccine administration within two weeks preceding the study procedure
• Currently pregnant
• Currently taking any prescribed medication other than oral contraceptives
• Treatments for weight loss or any other supplements that may alter weight or metabolism are not acceptable (vitamins are acceptable)
• Has consumed nicotine (smoking, inhaling, ingesting) within the last within the last 6 months
• Has used illicit drugs within the last 6 months
• Any medical, psychological, or social condition that, in opinion of principle investigators, would jeopardize the health or well-being of the participant during the study procedure or integrity of the data

Sponsors & Collaborators

• Rockefeller University: lead
• Beth Israel Deaconess Medical Center: collaborator

Study Sites (1)

The Rockefeller University Hospital

New York, New York, 10065, United States

Location

Study Officials

• Kaja Plucinska, PhD

  The Rockefeller University

  PRINCIPAL INVESTIGATOR

• Paul Cohen, PhD

  The Rockefeller University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2021
• First Posted: September 20, 2021
• Study Start: October 12, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)