Related Experiment Video
Updated: Jun 16, 2026
04:54
Using a Combination of Indirect Calorimetry, Infrared Thermography, and Blood Glucose Levels to Measure Brown Adipose Tissue Thermogenesis in Humans
Published on: June 2, 2023
Increased Brown Adipose Tissue Thermogenesis in Phenylketonuria
Noemí López-Rey1,2,3, Alba Cabaleiro1,4, María P Pata5
1Department of Physiology, CIMUS University of Santiago de Compostela Santiago de Compostela Spain.
Medcomm
|June 15, 2026
Summary
Phenylketonuria (PKU) elevates phenylalanine, surprisingly enhancing brown adipose tissue (BAT) activity. This metabolic shift is driven by fibroblast growth factor 21 (FGF21), impacting energy balance.
Area of Science:
- Metabolic Disorders
- Endocrinology
- Thermogenesis
Background:
- Phenylketonuria (PKU) is a common genetic disorder of amino acid metabolism, leading to neurological issues due to high phenylalanine (Phe) levels.
- Previous reports suggest altered metabolic rate and thermoregulation in PKU, but the role of brown adipose tissue (BAT) was unclear.
Purpose of the Study:
- To investigate brown adipose tissue (BAT) activity in individuals with PKU and related conditions.
- To explore the relationship between BAT temperature, metabolic parameters, and hormonal factors in PKU.
- To elucidate the underlying mechanisms of altered thermogenesis in PKU.
Main Methods:
- Noninvasive infrared thermography to measure BAT temperature in children and adolescents with PKU, mild hyperphenylalaninemia (MHPA), and controls.
- Analysis of circulating metabolic and hormonal parameters.
- Central administration of fibroblast growth factor 21 (FGF21) in rodent models (rats and mice).
- Analysis of public single-cell RNA-sequencing data.
Main Results:
- Individuals with PKU showed significantly higher BAT temperature compared to controls and MHPA patients, despite overall normothermia.
- PKU-associated higher BAT temperature correlated with elevated fibroblast growth factor 21 (FGF21) and thyroid hormones.
- Central FGF21 administration in rodents induced BAT thermogenesis, reduced hypothalamic AMP-activated protein kinase (AMPK) activity, and increased sympathetic drive to BAT.
- Hypothalamic neuronal populations showed convergent signaling for AMPK, thyroid hormone receptor, and FGF21 receptor.
Conclusions:
- PKU is associated with enhanced brown adipose tissue (BAT) thermogenesis.
- Elevated phenylalanine in PKU induces FGF21 production, which disrupts energy homeostasis by inhibiting hypothalamic AMPK.
- These findings reveal a novel mechanism linking a metabolic disorder to altered thermogenesis and energy balance.
![Visualization and Quantification of Brown and Beige Adipose Tissues in Mice using [18F]FDG Micro-PET/MR Imaging](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F62460.jpg&w=3840&q=50)
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