The Physiology of Human Brown Adipose Tissue

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Physiology of Human Brown Adipose Tissue

Conditions
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Adipose Tissue, Brown, Adipose Tissue, Obesity

Intervention / Treatment
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* Procedure: Fat biopsy
* Diagnostic Test: Blood sampling
* Genetic: Blood sample for DNA analysis


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 1. Healthy participants between age 18 and 75 years undergoing planned clinically indicated procedure at BIDMC. Exclusion Criteria: Body mass index (BMI) greater than or equal to 40 kg/m2 History of any local or systemic infectious disease with fever or requiring antibiotic within four weeks of drug administration; Diabetes, either previously diagnosed or hemoglobin A1c greater than or equal to 6.5% Use of oral or parenteral corticosteroids (epidural permitted) or other medication known to cause insulin resistance in the previous 6 weeks. Willingness to provide informed consent and follow study procedures, including attending scheduled visits. Chronic kidney disease stage 4 or 5 (including end-stage renal disease); 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; Active malignancy (except squamous or basal cell carcinoma of skin) Bleeding disorder, treatment with anticoagulants (if not discontinued prior to surgery), or platelet count <50,000; Current addiction to alcohol or substances of abuse; Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation; Use of an investigational drug within 30 days prior to screening. 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. Because the goal is to study adult human brown adipose tissue, children are not eligible to participate.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Surgical Participants<br>Individuals undergoing abdominal surgery or radiologically-guided biopsies for clinical indications will be recruited prior to the planned procedures. | Procedure: Fat biopsy<br>* 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.<br>Diagnostic Test: Blood sampling<br>* 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).<br>Genetic: Blood sample for DNA analysis<br>* Targeted resequencing of DNA to identify variants associated with adipose phenotypes will be performed.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human Cell Atlas