A Feedforward Loop within the Thyroid-Brown Fat Axis Facilitates Thermoregulation

Sci Rep. 2020 Jun 15;10(1):9661. doi: 10.1038/s41598-020-66697-0.


Thyroid hormones (TH) control brown adipose tissue (BAT) activation and differentiation, but their subsequent homeostatic response following BAT activation remains obscure. This study aimed to investigate the relationship between cold- and capsinoids-induced BAT activation and TH changes between baseline and 2 hours post-intervention. Nineteen healthy subjects underwent 18F-fluorodeoxyglucose positron-emission tomography (18F-FDG PET) and whole-body calorimetry (WBC) after 2 hours of cold exposure (~14.5 °C) or capsinoids ingestion (12 mg) in a crossover design. Standardized uptake values (SUV-mean) of the region of interest and energy expenditure (EE) were measured. Plasma free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) were measured before and 2 hours after each intervention. Subjects were divided into groups based on the presence (n = 12) or absence (n = 7) of BAT after cold exposure. 12 of 19 subjects were classified as BAT-positive. Subjects with BAT had higher baseline FT3 concentration, baseline FT3/FT4 ratio compared with subjects without BAT. Controlling for body fat percentage, FT3 concentration at baseline was associated with EE change from baseline after cold exposure (P = 0.037) and capsinoids (P = 0.047). Plasma FT4 level significantly increased associated with reciprocal decline in TSH after acute cold exposure and capsinoids independently of subject and treatment status. Circulating FT3 was higher in BAT-positive subjects and was a stronger predictor of EE changes after cold exposure and capsinoids in healthy humans. BAT activation elevates plasma FT4 acutely and may contribute towards augmentation of thermogenesis via a positive feedback response.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / diagnostic imaging
  • Adipose Tissue, Brown / metabolism*
  • Adult
  • Calorimetry
  • Capsaicin / administration & dosage
  • Capsaicin / analogs & derivatives*
  • Capsaicin / pharmacology
  • Cold Temperature
  • Cross-Over Studies
  • Feedback, Physiological
  • Female
  • Fluorodeoxyglucose F18 / administration & dosage
  • Humans
  • Male
  • Positron Emission Tomography Computed Tomography
  • Thermogenesis* / drug effects
  • Thyroid Gland / metabolism*
  • Thyrotropin / blood
  • Thyroxine / blood
  • Triiodothyronine / blood
  • Young Adult


  • Triiodothyronine
  • Fluorodeoxyglucose F18
  • Thyrotropin
  • Thyroxine
  • Capsaicin