Diurnal variations of brown fat thermogenesis and fat oxidation in humans

Diurnal variations in whole-body energy expenditure (EE) are influenced by physical activity and food intake. Studies indicate higher thermic effect of food (diet-induced thermogenesis, DIT) in the morning. This may explain links between meal timing and obesity, as breakfast skipping and night eating are associated with increased body fat. Brown adipose tissue (BAT) is crucial for nonshivering thermogenesis (NST) in rodents. Human BAT activation by cold exposure increases EE and fatty acid oxidation, influencing body fat. Previous research showed DIT is significantly higher in individuals with metabolically active BAT. This study investigated whether BAT contributes to diurnal variations in DIT, focusing on DIT and fat oxidation (FO) after breakfast, lunch, and dinner (Study 1), and cold-induced responses of EE and skin temperature (Study 2) to explore diurnal BAT activity variations.

Existing literature highlights diurnal variations in postabsorptive resting metabolic rate and diet-induced thermogenesis, with higher values observed in the morning. Meal timing is linked to obesity and metabolic disorders, potentially due to decreased DIT and daily EE. The mechanism for these diurnal variations is unclear but may involve the circadian system. Brown adipose tissue (BAT) is the primary site of nonshivering thermogenesis in rodents, and its rediscovery in adult humans has shown its role in increasing EE and fatty acid oxidation, impacting body fat regulation. Previous research suggests BAT's significant contribution to DIT in humans. These studies provide the foundation for investigating BAT's involvement in diurnal variations of energy metabolism.

Study 1 involved 21 healthy men (8 Low-BAT, 13 High-BAT) assessed via 18F-FDG PET/CT. 24-hour calorimetric measurements were conducted, with standardized meals at 9:00 am (breakfast), 2:00 pm (lunch), and 7:00 pm (dinner). Energy expenditure (EE), respiratory quotient (RQ), fat oxidation, and carbohydrate oxidation were calculated. Diet-induced thermogenesis (DIT) was determined. Study 2 included 23 healthy men (8 Low-BAT, 15 High-BAT) assessed by 18F-FDG PET/CT. Whole-body EE and skin temperature were measured at 27°C and after 90 min of cold exposure (19°C) in the morning and evening. Cold-induced thermogenesis (CIT) and cold-induced fat oxidation were calculated. Skin temperature in the supraclavicular region (Tscv) and a control chest region (Tc) was measured via infrared thermography. Statistical analysis used Student's t-tests and ANOVA for repeated measures.

Study 1 revealed higher DIT and FO after breakfast in the High-BAT group compared to the Low-BAT group. In the High-BAT group, FO was significantly higher after breakfast than after dinner. Study 2 demonstrated that cold-induced increases in EE, FO, and the temperature difference (Tscv-Tc) were significantly higher in the High-BAT group in the morning than in the evening. The morning CIT tended to be higher in the High-BAT group than in the evening (P = 0.056). Cold-induced fat oxidation was higher in the morning for the High-BAT group. The difference in Tscv and Tc (DTscv-c) after cold exposure was significantly larger in the High-BAT group in the morning, indicating greater BAT activation.

The findings support the hypothesis that human BAT activity exhibits diurnal variations, with higher activity in the morning. This is consistent with the higher DIT and fat oxidation observed in the morning in the High-BAT group. The diurnal variation in BAT activity may contribute to the association between meal timing and obesity. Breakfast skipping or night eating might lead to less BAT activation, decreased fat oxidation, and increased body fat accumulation. The diurnal rhythm in BAT activity may be influenced by an intrinsic cell-autonomous circadian mechanism, the sympathetic nervous system (SNS), glucocorticoids, or the diurnal changes in responsiveness of BAT to these factors. Further studies are needed to clarify the precise mechanisms.

This study demonstrates diurnal variations in human BAT activity, with higher activity in the morning. This may partly explain the association between meal timing and obesity. The findings highlight the importance of breakfast consumption and suggest that time-restricted feeding strategies may be more effective when timed to align with the peak of BAT activity in the morning.

The study was conducted on healthy men only, limiting the generalizability to other populations (women, older adults, individuals with metabolic disorders). The use of surrogates for BAT activity (CIT, Tscv-Tc) instead of repeated FDG-PET/CT scans might introduce some measurement error. Further research is needed to investigate the underlying mechanisms driving the diurnal rhythm in BAT activity and the effects of different meal-timing interventions.