Diurnal variations of brown fat thermogenesis and fat oxidation in humans

Whole-body energy expenditure (EE) exhibits diurnal variations largely driven by physical activity and food intake. Prior studies report higher diet-induced thermogenesis (DIT) in the morning than in the evening/night, potentially linking meal timing to obesity risk; breakfast skipping and night eating may reduce DIT and daily EE. The mechanisms underlying diurnal DIT variation in humans are unclear. Brown adipose tissue (BAT), the main site of nonshivering thermogenesis (NST), is activated by cold and contributes to increases in whole-body EE and fatty acid oxidation, thereby regulating body fat. BAT also contributes to DIT in humans, as DIT is higher in subjects with active BAT and postprandial BAT activation has been demonstrated by PET/CT with appropriate tracers. The authors hypothesized that BAT contributes to the diurnal variations of DIT. They reanalyzed prior 24 h EE data to focus on DIT and fat oxidation (FO) after breakfast, lunch, and dinner (STUDY 1). In a separate study (STUDY 2), they examined whether human BAT exhibits diurnal variation in vivo by measuring cold-induced responses of whole-body EE and supraclavicular skin temperature (proximal to BAT) in the morning and evening. The study aims to determine if BAT activity is higher in the morning and whether this underlies higher DIT and FO earlier in the day.

Design: Two studies in healthy men assessing BAT activity by 18F-FDG PET/CT and measuring energy metabolism across times of day. Participants: STUDY 1 included 21 healthy men (20–50 years; BMI 18.0–24.9 kg/m²), divided by PET/CT into Low-BAT (visually undetectable; SUVmax 1.1±0.4; n=8) and High-BAT (detectable; SUVmax 8.5±4.8; n=13). STUDY 2 included 23 healthy men (20–29 years; BMI 19.3–24.1 kg/m²), Low-BAT (SUVmax 0.79±0.47; n=8) and High-BAT (SUVmax 8.04±4.74; n=15). BAT assessment (both studies): After 10–12 h fast, mild cold exposure at 19 °C for 2 h (with intermittent towel-wrapped ice to soles). 18F-FDG administered after 1 h; PET/CT scan 1 h later at 24 °C. BAT presence assessed visually; semiquantitative uptake measured as SUVmax (threshold 2.00). Body composition: DXA or multifrequency bioelectrical impedance. STUDY 1 procedures: 24 h whole-room indirect calorimetry (start 0000 h). Entry 1900 h; sleep 0000–0700 h; low-intensity activity 0715–0900 h; free activity thereafter at 27.0±0.2 °C, 50±3% RH. Standardized meals at 0900 (breakfast), 1400 (lunch), 1900 (dinner), with 15 E% protein, 25 E% fat, 60 E% carbohydrate; energy individualized (BMR×1.3). Gas analysis by mass spectrometry; EE, respiratory quotient (RQ), fat and carbohydrate oxidation calculated (including urinary nitrogen). DIT estimated by plotting total EE against physical activity (Schutz method), and computed for 5 h periods post each meal. STUDY 2 procedures: Indirect calorimetry with ventilated hood at 27 °C and after 90 min at 19 °C in morning (0800–1100 h) and evening (1900–2200 h) after 11–13 h fast. Oxygen consumption and CO2 production recorded; steady-state final 10 min used. RQ, EE, fat and carbohydrate oxidation calculated; protein oxidation assumed constant (21.4% of resting EE at 27 °C) during mild cold. Cold-induced thermogenesis (CIT) and cold-induced fat oxidation computed as differences (19 °C minus 27 °C). Infrared thermography measured supraclavicular (Tscv) and chest control (Tc) skin temperatures; difference DTscv-c used as surrogate of BAT thermogenesis. Statistical analysis: Values mean±SD. Group differences by Student’s t tests. Repeated-measures ANOVA with within-subject factor clock time and between-subject factor BAT group for EE, DIT, RQ, FO, skin temperature, CIT, and cold-induced FO. Tukey post hoc tests. Significance P<0.05.

• STUDY 1 (24 h calorimetry at 27 °C):
  • Total daily DIT (%) over 15 h (0900–2359 h) was higher in High-BAT vs Low-BAT (P<0.05). DIT (kcal/d) tended to be higher in High-BAT.
  • Postprandial DIT (5 h windows): High-BAT vs Low-BAT after breakfast: 10.3±2.7% vs 6.9±3.9% (P<0.05); after lunch also higher in High-BAT (P<0.05); after dinner not significantly different (9.3±3.2% vs 6.7±4.1%; P=0.122).
  • Within High-BAT, DIT did not differ significantly among breakfast, lunch, dinner; in all subjects, DIT higher after breakfast vs lunch.
  • 24 h RQ lower in High-BAT vs Low-BAT (P<0.05). After breakfast, RQ in High-BAT 0.869±0.029 vs higher after lunch (0.881±0.032; P<0.01) and dinner (0.880±0.032; P=0.05). Between groups, RQ lower in High-BAT after breakfast and dinner (P<0.05), trend after lunch (P=0.051).
  • 24 h fat oxidation higher in High-BAT vs Low-BAT (P<0.05).
  • FO after breakfast (5 h) in High-BAT 15.6±5.1 g vs Low-BAT 10.2±3.0 g (P<0.05). Within High-BAT, FO breakfast > lunch (11.7±5.5 g; P<0.01) and > dinner (11.8±6.0 g; P=0.01). Between groups, FO differences not significant after lunch (P=0.143) or dinner (P=0.102).
  • Carbohydrate oxidation lower in High-BAT vs Low-BAT irrespective of meal timing (P<0.05); no significant diurnal differences.
• STUDY 2 (mild cold, morning vs evening):
  • Morning EE at 27 °C similar between groups; at 19 °C increased more in High-BAT vs Low-BAT (P<0.05). Evening EE at 27 °C and 19 °C showed no group differences.
  • CIT (19 °C minus 27 °C): morning High-BAT 152±167 kcal/d vs Low-BAT −10±133 kcal/d (P<0.05); evening High-BAT 75±154 vs Low-BAT 36±155 kcal/d (ns). In High-BAT, morning CIT tended to exceed evening (P=0.056).
  • Cold-induced fat oxidation (19 °C minus 27 °C): morning High-BAT 1.32±0.78 g vs Low-BAT 0.02±0.83 g (P<0.01); evening High-BAT 0.48±1.60 g vs Low-BAT 0.31±1.21 g (ns).
  • Skin temperature indices: At 27 °C, Tscv > Tc by 0.35–0.41 °C. After cold, DTscv-c at 19 °C larger in High-BAT than Low-BAT irrespective of time (P<0.01). In High-BAT, DTscv-c at 19 °C was higher in morning (1.37±0.29 °C) than evening (1.17±0.39 °C; P<0.01); in Low-BAT, morning and evening similar (~0.79–0.80 °C).
• Overall: BAT-associated NST and fat oxidation are evident in the morning but not evening, indicating higher BAT activity in morning; aligns with higher DIT and FO after breakfast.

The findings support that human BAT exhibits diurnal variation, being more active in the morning. In Study 1, individuals with active BAT showed higher DIT and fat oxidation after breakfast (and to a lesser extent lunch) than dinner, alongside lower RQ and higher 24 h fat oxidation. Study 2 corroborated higher morning BAT thermogenic responses: greater cold-induced thermogenesis, fat oxidation, and supraclavicular skin temperature preservation in High-BAT individuals, with negligible diurnal differences in Low-BAT. These diurnal patterns are consistent with rodent data showing circadian rhythms in BAT thermogenic function and expression of key genes (e.g., UCP1) and clock components. Potential mechanisms include central circadian regulation via the ventromedial hypothalamus and sympathetic outflow to BAT, and endocrine modulation such as the morning cortisol surge acutely stimulating BAT. BAT preferentially oxidizes fatty acids; the observed higher morning fat oxidation may reflect circadian regulation of substrate utilization, potentially involving transcriptional regulators like KLF15 and links to amino acid metabolism (e.g., BCAA utilization by BAT). Clinically, higher morning BAT activity may partially explain adverse metabolic associations with breakfast skipping and late-night eating, and suggests that aligning food intake earlier in the day (e.g., morning-focused time-restricted feeding) could better harness BAT thermogenesis and improve metabolic outcomes.

In healthy men, nonshivering thermogenesis and fat oxidation linked to BAT are higher in the morning than in the evening. High-BAT individuals display greater DIT and fat oxidation after breakfast and enhanced cold-induced increases in EE and fat oxidation in the morning, along with larger supraclavicular thermographic responses, indicating a diurnal rhythm of BAT activity. These findings provide a physiological basis for the influence of meal timing on body fatness and metabolic health and suggest that earlier-day eating patterns (e.g., consuming breakfast, morning/daytime time-restricted feeding) may better engage BAT. Future research should elucidate the neuroendocrine and molecular mechanisms of human BAT circadian regulation, assess generalizability across sexes and age groups, and test interventions leveraging timing to optimize BAT activation.

• Repeated PET/CT at different times of day—the gold standard for assessing diurnal BAT activity—was not feasible due to radiation exposure; surrogate measures (cold-induced EE, fat oxidation, and supraclavicular skin temperature) were used instead.
• Samples comprised healthy young men; results may not generalize to women, older adults, or individuals with metabolic disease.
• Modest sample sizes may limit power to detect smaller diurnal effects (e.g., CIT morning vs evening trend P=0.056).