The Physiology of Human Brown Adipose Tissue

Recruiting

• Conditions: Adipose Tissue, Brown; Adipose Tissue; Obesity
• Interventions: Procedure: Fat biopsy; Diagnostic Test: Blood sampling; Genetic: Blood sample for DNA analysis

• Registration Number: NCT04352244
• Lead Sponsor: Beth Israel Deaconess Medical Center

Brief Summary

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.

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 Timeline

• Study Start: 2020-03-05
• Study First Submitted: 2020-03-31
• Study First Submitted QC: 2020-04-15
• Study First Posted: 2020-04-20
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-07
• Last Update Posted: 2024-08-09
• Primary Completion: 2027-06-30
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Not provided

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Surgical Participants	Blood sample for DNA analysis	Individuals undergoing abdominal surgery or radiologically-guided biopsies for clinical indications will be recruited prior to the planned procedures.
Surgical Participants	Fat biopsy	Individuals undergoing abdominal surgery or radiologically-guided biopsies for clinical indications will be recruited prior to the planned procedures.
Surgical Participants	Blood sampling	Individuals undergoing abdominal surgery or radiologically-guided biopsies for clinical indications will be recruited prior to the planned procedures.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
DNA analysis	March 2022	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).

Trial Locations

Locations (1)

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States