Background Cold exposure mobilizes lipids to feed thermogenic processes in organs, including brown adipose tissue (BAT), and thereby increases metabolic rate. In rodents, BAT metabolic activity exhibits a pronounced diurnal rhythm, which is highest at the start of the wakeful period. We now aimed to investigate whether cold-induced thermogenesis displays diurnal variation in humans, and differs between males and females.

Methods We performed a randomized crossover study in which fasted young and lean males (n=12; 22.8±3.6 years old; BMI: 22.0±2.0 kg/m2) and females (n=12; 21.4±3.1 years old; BMI: 22.5±2.0 kg/m2) underwent a 2.5-hour personalized cooling protocol using water-perfused mattresses in the morning (7:45 AM) and evening (7:45 PM), with one day in between. Cold-induced thermogenesis was assessed by determining energy expenditure (EE) and supraclavicular skin temperature. Blood samples were taken at six sequential time points during cooling.

Results In males, cold-induced EE was higher in the morning than in the evening (+54±10% vs. +30±7%, P=0.05). By contrast, cold-induced EE did not differ between the morning and the evening in females (+37±9% vs. +30±10%, P=0.42). Additionally, only in males, supraclavicular skin temperature upon cold increased more in the morning than in the 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 cold in the morning, but not in the 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 the morning, than in the evening.

Conclusion Cold-induced thermogenesis is higher in the morning than in the evening in males, however, lipid metabolism is more modulated in the morning than in the evening in females. We anticipate that diurnal variations should be considered when targeting thermogenic tissues, such as BAT, to improve cardiometabolic health.