Cold-Induced Thermogenesis Shows a Diurnal Variation That Unfolds Differently in Males and Females

Abstract

Context: Cold exposure mobilizes lipids to feed thermogenic processes in organs, including brown adipose tissue (BAT). In rodents, BAT metabolic activity exhibits a diurnal rhythm, which is highest at the start of the wakeful period.

Objective: We investigated whether cold-induced thermogenesis displays diurnal variation in humans and differs between the sexes.

Methods: This randomized crossover study included 24 young and lean male (n = 12) and female (n = 12) participants who underwent 2.5-hour personalized cooling using water-perfused mattresses in the morning (7:45 am) and evening (7:45 pm), with 1 day in between. We measured energy expenditure (EE) and supraclavicular skin temperature in response to cold exposure.

Results: In males, cold-induced EE was higher in the morning than in the evening (+54% ± 10% vs +30% ± 7%; P = 0.05) but did not differ between morning and evening in females (+37% ± 9% vs +30% ± 10%; P = 0.42). Only in males, supraclavicular skin temperature upon cold increased more in morning than evening (+0.2 ± 0.1 °C vs -0.2 ± 0.2 °C; P = 0.05). In males, circulating free fatty acid (FFA) levels were increased after morning cold exposure, but not evening (+90% ± 18% vs +9% ± 8%; P < 0.001). In females, circulating FFA (+94% ± 21% vs +20% ± 5%; P = 0.006), but also triglycerides (+42% ± 5% vs +29% ± 4%, P = 0.01) and cholesterol levels (+17% ± 2% vs 11% ± 2%; P = 0.05) were more increased after cold exposure in morning than in evening.

Conclusion: Cold-induced thermogenesis is higher in morning than evening in males; however, lipid metabolism is more modulated in the morning than the evening in females.

Trial registration: ClinicalTrials.gov NCT04406922.

Keywords: brown adipose tissue; cardiometabolic health; circadian rhythm; cold stimulus; gender differences; metabolism.

© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.

Figures

Figure 1.

Timeline of the study procedures performed both days. Participants lay in bed between 2 water-perfused mattresses with an initial temperature of 32 °C (considered thermoneutral; mattresses temperature is indicated with the purple solid line). After 45 minutes, temperature was gradually decreased with 5 °C increments until shivering occurred or until the minimum temperature of 9 °C was reached. Then, the stable cold phase started. Before and after cold, an infrared thermographic picture was made. Blood was drawn at the end of thermoneutrality (indicated with the drop icon), after 15 minutes of cooling down, at the onset of shivering and at 3 time points during the stable cold phase. Energy expenditure (indicated with the yellow rectangle) was assessed during the thermoneutral phase, during cooling down and during the last 30 minutes of the stable cold phase (from +60 minutes until the end of cooling) using indirect calorimetry. Skin temperatures were measured every minute using iButtons. For analyses concerning skin temperature, the last 5 minutes of the thermoneutral phase, the 5 minutes after the first 10 minutes of cooling down, the 5 minutes before shivering, and the last 5 minutes of the stable cold phase were averaged (indicated with the thermometer icon).

Figure 2.

The time until shivering and the shiver- and stable cold temperatures during cold exposure in the morning vs the evening in males and females. From left to right: the time from the start of the personalized cooling until shivering occurred, the water temperature at the moment of shivering, and the water temperature at the end of cooling, in males (A) and in females (B). A paired Student’s t test was used to compare the morning and the evening. *P < 0.05, **P < 0.01.

Figure 3.

Increase in energy expenditure during cold exposure in the morning vs the evening in males and females. Energy expenditure (EE) was assessed during the thermoneutral phase, the cooling down phase and the stable cold phase (the latter was divided into 2 parts: the first part starting at +60 minutes and the second part until the end of cooling). The cold-induced change in EE was calculated as the percentual change in EE from thermoneutrality to the end of cooling. Top panel shows results in males (A), bottom panel shows results in females (B). General linear model with repeated measures was used to test for an interaction between the effect of cold over time and the moment of the day (ie, morning vs evening [M vs E]), a paired Student’s t test was used to compare the cold-induced change in EE between the morning and the evening. Abbreviation: TN = thermoneutral.

Figure 4.

Changes in supraclavicular skin temperature during cold exposure in the morning vs the evening in males and females. Supraclavicular skin temperature was measured using wireless iButtons during the last 5 minutes of the thermoneutral phase, during the cooling down phase, right before shivering occurred, and during the last 5 minutes of the stable cold phase (“end cooling”). The Δ temperature was calculated as the change in supraclavicular temperature from thermoneutrality to the end of cooling. Top panel shows results in males (A), bottom panel shows results in females (B). General linear model with repeated measures was used to test for an interaction between the effect of cold over time and the moment of the day (ie, morning vs evening [M vs E]), a paired Student’s t test was used to compare the cold-induced EE in the morning vs in the evening. Abbreviation: TN = thermoneutral.