The Physiology of Human Brown Adipose Tissue

Brown fat is a type of fat, found in both children and adults, which can produce heat and regulate the body's metabolism and energy use. White fat is the more common type of fat which is used to store extra calories. Understanding more about differences between brown and white fat may allow us to develop new approaches to improve the body's metabolism.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Adipose Tissue; Adipose Tissue, Brown
• Intervention / Treatment: Procedure: Fat biopsy; Diagnostic test: Blood sampling; Genetic: Blood sample for DNA analysis

Detailed Description

The overarching goal of this study, is to map fat (adipose) tissue differences in humans. The investigators will probe multiple aspects of fat cell (adipocyte) identity by integrating quantitative chemical imaging, single-cell and single-nucleus RNA sequencing (sc and snRNAseq), and site-specific collection of adipocytes and adipocyte precursors.

Deidentified data from these studies will be submitted to the Human Cell Atlas. The investigators anticipate that these studies will ultimately increase understanding of mechanisms by which fat (adipose) tissue regulates systemic metabolism (energy transformation in the body), and promotes risk for metabolic disease. Knowledge gained from this research may be used to set the stage for disease-specific analyses, and aid in the development of personalized medicine for metabolic diseases such as type 2 diabetes.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Amanda L Sheehan, MSN; Phone Number: 6173092695; Email: amanda.sheehan@joslin.harvard.edu
• Study Contact Backup: Name: Mary Elizabeth Patti, MD; Phone Number: 6173092635; Email: MaryElizabeth.Patti@joslin.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: Andrew P White, MD; Phone Number: 6177549000; Email: apwhite@bidmc.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Participants planning a procedure will be recruited from clinical practices of Dr. Andrew White, Dr. Peter Mowschenson, and Dr. Per-Olof Hasselgren at BIDMC.

Description

Inclusion criteria:

1. Healthy participants between age 18 and 75 years undergoing planned clinically indicated procedure at BIDMC.

Exclusion Criteria:

1. Body mass index (BMI) greater than or equal to 40 kg/m2
2. History of any local or systemic infectious disease with fever or requiring antibiotic within four weeks of drug administration;
3. Diabetes, either previously diagnosed or hemoglobin A1c greater than or equal to 6.5%
4. Use of oral or parenteral corticosteroids (epidural permitted) or other medication known to cause insulin resistance in the previous 6 weeks.
5. Willingness to provide informed consent and follow study procedures, including attending scheduled visits.
6. Chronic kidney disease stage 4 or 5 (including end-stage renal disease);
7. Hepatic disease, including serum alanine aminotransferase (ALT) or aspartate transaminase (AST) greater than or equal to 3 times the upper limit of normal; hepatic synthetic insufficiency as defined as serum albumin < 3.0 g/dL; or serum bilirubin > 2.0;
8. Active malignancy (except squamous or basal cell carcinoma of skin)
9. Bleeding disorder, treatment with anticoagulants (if not discontinued prior to surgery), or platelet count <50,000;
10. Current addiction to alcohol or substances of abuse;
11. Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation;
12. Use of an investigational drug within 30 days prior to screening.
13. There will be no involvement of special vulnerable populations such as fetuses, neonates, pregnant women, children, prisoners, institutionalized or incarcerated individuals, or others who may be considered vulnerable populations.
14. Because the goal is to study adult human brown adipose tissue, children are not eligible to participate.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Surgical Participants; Individuals undergoing abdominal surgery or radiologically-guided biopsies for clinical indications will be recruited prior to the planned procedures.

Procedure: Fat biopsy; The fat biopsy is performed during a scheduled procedure at the Beth Israel Deaconess Medical Center (BIDMC). Routine preoperative procedures will be followed, including local anesthesia (numbing a particular region of the body) or general anesthesia (being put to sleep). Adipose tissue will be sampled from different depots depending on the procedure. For example, the surgeon will collect adipose tissue from the neck and supraclavicular depots from cervical spine, thyroid, and parathyroid procedures; perinephric fat from adrenalectomies, omental fat from abdominal procedures, and paraspinal fat from lumbar spine procedures. Up to 5 pieces of fat tissue weighing about three to six grams will be removed. All other aspects of the surgical procedure will proceed as planned. Samples will be prepared for subsequent laboratory analysis.; Diagnostic test: Blood sampling; A blood sample will be collected in the fasting state either during preoperative testing or in the preoperative area on the day of planned procedure for measurement of adipose functional markers (leptin, adiponectin) and insulin resistance (insulin, C-peptide), and measures of glycemia (glucose, hemoglobin A1c).; Genetic: Blood sample for DNA analysis; Targeted resequencing of DNA to identify variants associated with adipose phenotypes will be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Collect human brown and white adipose tissue to prepare progenitor and differentiated cells for single nucleus RNA analysis.	Adipose tissue biopsy samples will be processed for single-nucleus RNA analysis of gene expression.	March 2022
Collect human brown and white adipose tissue to prepare progenitor and differentiated cells for Raman spectroscopy.	Adipose tissue biopsy samples will be processed for Raman spectroscopy analysis.	March 2022
Collect human brown and white adipose tissue to prepare cells for ex vivo differentiation	Adipose tissue biopsy samples will be processed for ex vivo differentiation.	March 2022
Insulin resistance	Insulin resistance of participants, assessed by homeostatic model of insulin resistance (HOMA-IR), will be analyzed and summarized.	March 2022
Hemoglobin A1c	Hemoglobin A1c levels for participants will be analyzed and summarized.	March 2022
Fasting glucose levels	Fasting glucose levels for participants will be analyzed and summarized.	March 2022
Body mass index (BMI)	Weight and height will be combined to report BMI in kg/m^2. BMI of participants will be analyzed and summarized.	March 2022
Demographic characteristics	Demographic characteristics of participants will be analyzed and summarized.	March 2022

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DNA analysis	DNA will be isolated and stored from blood samples. If specific genes are differentially regulated as a function of metabolic state or anatomical location of biopsy, locus-specific or genome-wide genotyping may be performed to assess potential regulatory single-nucleotide polymorphisms (SNP).	March 2022

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: Joslin Diabetes Center; Chan Zuckerberg Initiative
• Investigators: Principal Investigator: Mary Elizabeth Patti, MD, Joslin Diabetes Center

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2020
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: March 31, 2020
• First Submitted That Met QC Criteria: April 15, 2020
• First Posted (Actual): April 20, 2020

Study Record Updates

• Last Update Posted (Estimated): October 31, 2025
• Last Update Submitted That Met QC Criteria: October 30, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Human Cell Atlas
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: 2009P-000101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified participant data will be shared with other researchers with permission of local institutional review boards via the Human Cell Atlas database.
• IPD Sharing Time Frame: 6 months after publication of study results
• IPD Sharing Access Criteria: Data will be shared with academic investigators with approval of local institutional review boards.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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