# The Interaction Between the Thyroid Axis and Brown Adipose Tissue in Humans

> **NIH NIH R03** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2024 · $145,636

## Abstract

This project is designed to evaluate the relationship between the intra-cellular thyroid hormone (TH) levels and
brown adipose tissue (BAT) activity, transcriptome and cellular composition and correlate with circulating TH
levels and other metabolic parameters in adult humans, to better understand the interaction between the
thyroid axis and BAT in the process of thermogenesis and energy expenditure. Studies using positron emission
tomography/ computed tomography (PET/CT) scanning have shown metabolically active BAT in adult humans,
whose activity correlated inversely with body fat. TH plays an important role in brown adipocyte differentiation
and controls adaptive thermogenesis in BAT by uncoupling the oxidative phosphorylation. Based on data from
animal studies and findings from our prior studies in adult humans, we hypothesize that intra-cellular T3, the
active form of TH stimulates BAT activity by directly affecting the transcriptome and cellular composition of
BAT.
We plan to study 10 hyperthyroid and 10 hypothyroid patients who require thyroid surgery as part of their standard
medical care. Perithyroidal BAT and subcutaneous white adipose tissue (WAT) (control) will be collected during
the surgery. Thyroid function tests and metabolic parameters, including fasting glucose, insulin, HbA1c, and lipid
panel will be measured at the time of the surgery. A study visit will be scheduled in the Clinical Research
Center (CRC) within a week prior to the thyroid surgery. The patients will undergo indirect calorimetry to measure
resting metabolic rate (RMR) and dual energy xray absorptiometry (DXA) to measure body composition. A PET-
CT scan will then be performed after wearing a cooling vest set at 55-61 °F for 2 hours to measure BAT volume
and activity. We will measure adipose tissue TH concentration using liquid chromatography–mass spectrometry
(LC-MS). We will investigate the relationship between the intra-cellular and circulating thyroid hormone (TH)
levels and BAT activity, RMR, body composition as well as other metabolic parameters. We will also perform
block and single nucleus RNA-sequencing of the collected adipose tissue samples to understand the impact of
the thyroid axis on the transcriptome and cellular composition of human neck BAT and WAT.
The current project will help to further elucidate the complex relationship between the thyroid axis and BAT
function, transcriptome and cellular composition in the process of thermogenesis in humans. There are no prior
published human studies looking into the effect of intra-cellular TH levels on BAT activity. The study results will
be used to write a competitive NIH grant (R01) to experimentally test the connection between TH and BAT in
adult humans and find new treatment strategies for obesity and diabetes, which are major public health
concerns.

## Key facts

- **NIH application ID:** 10792044
- **Project number:** 1R03TR004808-01
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** ALINA GAVRILA-FILIP
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $145,636
- **Award type:** 1
- **Project period:** 2024-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10792044

## Citation

> US National Institutes of Health, RePORTER application 10792044, The Interaction Between the Thyroid Axis and Brown Adipose Tissue in Humans (1R03TR004808-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10792044. Licensed CC0.

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