Evaluation of metabolic and molecular characteristics in the white adipose tissue of cold-exposed animals

Abstract

Background

Cold exposure induces important physiological and metabolic adaptations in mammals, characterized by increased brown adipose tissue activity. Although genomic and molecular modulation is widely discussed within pathological contexts, the molecular responses and regulations of white adipose tissue under normal environmental variations, such as cooling thermal stress, still require further elucidation.

Cold exposure induces important physiological and metabolic adaptations in mammals, characterized by increased brown adipose tissue activity. Although genomic and molecular modulation is widely discussed within pathological contexts, the molecular responses and regulations of white adipose tissue under normal environmental variations, such as cooling thermal stress, still require further elucidation.

Objective

To evaluate the phenotypic, metabolic, and molecular changes in the adipose tissue of mice subjected to chronic and acute cold exposure.

To evaluate the phenotypic, metabolic, and molecular changes in the adipose tissue of mice subjected to chronic and acute cold exposure.

Methods

After the ethical approval (#6741-1/2025), male C57BL6/J mice were exposed or not to cold for 5 or 15 days. The control group was kept at 22 °C and the cold at 4 °C (N = 6). Epididymal adipose tissue was collected for Fads1/2 expression analysis, PPAR-alpha and gamma proteins content, histology, and fatty acid profile and quantification.

After the ethical approval (#6741-1/2025), male C57BL6/J mice were exposed or not to cold for 5 or 15 days. The control group was kept at 22 °C and the cold at 4 °C (N = 6). Epididymal adipose tissue was collected for Fads1/2 expression analysis, PPAR-alpha and gamma proteins content, histology, and fatty acid profile and quantification.

Results

The acute phase (5 days) was marked by weight stagnation and the onset of hyperphagia, with daily food intake approximately 8.3 g in the cold group compared to 3.9 g in the control group. This hyperphagia is driven by an increase in energy consumption, which leads to a significantly acute cumulative food intake (32.12 g vs. 20.46 g), translating into higher overall energy intake (107.6 kcal vs. 68.53 kcal). This hyperphagia consolidates in the prolonged phase (15 days), resulting in a significantly higher total cumulative food intake (105.90 g vs. 70.43 g) and higher total caloric intake in the cold group (∼328.2 kcal vs. 245.05 kcal). Despite this higher energy supply, the 15 day group showed a phenotypic reduction in the final body weight (21.59 g in the cold vs. 22.81 g in the control) and a depletion in epididymal fat (∼0.151 g vs. ∼0.302 g).

The acute phase (5 days) was marked by weight stagnation and the onset of hyperphagia, with daily food intake approximately 8.3 g in the cold group compared to 3.9 g in the control group. This hyperphagia is driven by an increase in energy consumption, which leads to a significantly acute cumulative food intake (32.12 g vs. 20.46 g), translating into higher overall energy intake (107.6 kcal vs. 68.53 kcal). This hyperphagia consolidates in the prolonged phase (15 days), resulting in a significantly higher total cumulative food intake (105.90 g vs. 70.43 g) and higher total caloric intake in the cold group (∼328.2 kcal vs. 245.05 kcal). Despite this higher energy supply, the 15 day group showed a phenotypic reduction in the final body weight (21.59 g in the cold vs. 22.81 g in the control) and a depletion in epididymal fat (∼0.151 g vs. ∼0.302 g).

Conclusion

Exposure to a temperature of 4 °C promotes a strong adaptive response that prioritizes energy expenditure and survival against inhospitable conditions, as evidenced by hyperphagia and the depletion of epididymal adipose tissue, suggesting the redirection of fats for oxidation in brown adipose tissue. As a next perspective, we are under development of evaluation of the gene expression of desaturases (Fads1/2) to understand whether the modulation of the adipose tissue lipid profile also acts in an integrated manner within this metabolic response.

Exposure to a temperature of 4 °C promotes a strong adaptive response that prioritizes energy expenditure and survival against inhospitable conditions, as evidenced by hyperphagia and the depletion of epididymal adipose tissue, suggesting the redirection of fats for oxidation in brown adipose tissue. As a next perspective, we are under development of evaluation of the gene expression of desaturases (Fads1/2) to understand whether the modulation of the adipose tissue lipid profile also acts in an integrated manner within this metabolic response.