Thermal Regulation in Metabolic Studies of Mice

Thermal regulation is a pivotal variable in metabolic research using mouse models. Owing to their small size and high surface area to volume ratio, mice exhibit a pronounced requirement for thermogenic responses to maintain core body temperature when housed below their thermoneutral zone (∼28–30 °C). Standard laboratory conditions (20–22 °C) impose mild cold stress that elevates basal energy expenditure, activates brown adipose tissue (BAT) and alters sympathetic nervous system output. These adaptations can confound interpretations of energy balance, glucose homeostasis and drug efficacy. A thorough understanding of how ambient temperature shapes metabolic phenotypes, from insulin sensitivity to adipose tissue function, is essential for improving the translational relevance of preclinical studies. Recent advances have elucidated molecular pathways governing adaptive thermogenesis, highlighted the impact of thermoneutral housing on metabolic disease models and underscored the need for standardised temperature regimes to align murine outcomes with human physiology.

Research from Nature Portfolio

Recent studies have demonstrated that targeted genetic manipulation of oxygen-sensing enzymes in adipocytes can overcome BAT dormancy at thermoneutrality. Selective deletion of the prolyl hydroxylase PHD2 in adipose tissue maintains elevated energy expenditure and enhances Ucp1-driven thermogenesis, even under conditions that normally suppress BAT activation. This work identifies adipose-PHD2 as a modulator of the hypoxia-inducible factor (HIF) pathway and proposes PHD inhibition as a therapeutic strategy for metabolic disorders. In a complementary vein, investigations into exercise training have revealed that housing mice at 30 °C markedly attenuates the insulin-sensitising and energy-expending benefits of physical activity observed at room temperature. Thermoneutral housing blunts sympathetic stimulation of muscle and adipose tissue, reducing improvements in body composition and resting metabolic rate. These findings underline the critical influence of ambient temperature on the outcomes of genetic and intervention studies.

Thermal Regulation in Metabolic Studies of Mice publication trend

The graph below shows the total number of articles in thermal regulation in metabolic studies of mice across all publications each year (not limited to Nature Index journals).

Technical terms

Thermoneutrality: The ambient temperature range at which energy expenditure for thermoregulation is minimised.

Brown adipose tissue (BAT): A specialised fat depot rich in mitochondria and Uncoupling Protein 1 that dissipates energy as heat.

Uncoupling Protein 1 (Ucp1): A mitochondrial carrier protein that facilitates proton leak and non-shivering thermogenesis.

Energy expenditure: The total energy used by an organism, including basal metabolism, activity and heat production.

Sympathetic drive: Activation of the sympathetic nervous system that regulates thermogenic and cardiovascular responses to temperature.

Insulin sensitivity: The efficiency with which cells respond to insulin to uptake and metabolise glucose.

References

1. Translational potential of mouse models of human metabolic disease. Cell (2024).
2. Adipocyte deletion of the oxygen-sensor PHD2 sustains elevated energy expenditure at thermoneutrality. Nature Communications (2024).
3. Housing temperature influences exercise training adaptations in mice. Nature Communications (2020).
4. Insulin at the intersection of thermoregulation and glucose homeostasis. Molecular Metabolism (2024).
5. Housing Temperature Impacts the Systemic and Tissue‐Specific Molecular Responses to Cancer in Mice. Journal of Cachexia Sarcopenia and Muscle (2025).
6. Thermoneutrality decreases thermogenic program and promotes adiposity in high‐fat diet‐fed mice. Physiological Reports (2016).
7. Optimal housing temperatures for mice to mimic the thermal environment of humans: An experimental study. Molecular Metabolism (2017).