Diurnal variations of brown fat thermogenesis and fat oxidation in humans

Abstract

Background/objectives Disturbed circadian rhythm is associated with an increased risk of obesity and metabolic disorders. Brown adipose tissue (BAT) is a site of nonshivering thermogenesis (NST) and plays a role in regulating whole-body energy expenditure (EE), substrate metabolism, and body fatness. In this study, we examined diurnal variations of NST in healthy humans by focusing on their relation to BAT activity. Methods Forty-four healthy men underwent 18F-fluoro-2-deoxy-D-glucose positron emission tomography and were divided into Low-BAT and High-BAT groups. In STUDY 1, EE, diet-induced thermogenesis (DIT), and fat oxidation (FO) were measured using a whole-room indirect calorimeter at 27 °C. In STUDY 2, EE, FO, and skin temperature in the region close to BAT depots (Tscv) and in the control region (Tc) were measured at 27 °C and after 90 min cold exposure at 19 °C in the morning and in the evening. Results In STUDY 1, DIT and FO after breakfast was higher in the High-BAT group than in the Low-BAT group (P < 0.05), whereas those after dinner were comparable in the two groups. FO in the High-BAT group was higher after breakfast than after dinner (P < 0.01). In STUDY 2, cold-induced increases in EE (CIT), FO, and Tscv relative to Tc in the morning were higher in the High-BAT group than in the Low-BAT group (P < 0.05), whereas those after dinner were comparable in the two groups. CIT in the High-BAT group tended to be higher in the morning than in the evening (P = 0.056). Conclusion BAT-associated NST and FO were evident in the morning, but not in the evening, suggesting that the activity of human BAT is higher in the morning than in the evening, and thus may be involved in the association of an eating habit of breakfast skipping with obesity and related metabolic disorders.

Brown adipose tissue–associated postprandial thermogenesis in humans: Different effects of isocaloric meals rich in carbohydrate, fat, and protein

“…Through simultaneous 24-hour recording of food intake and oxygen consumption in mice de cient of uncoupling protein 1 (UCP1), which is a key molecule for BAT thermogenesis, the role of BAT in DIT was proven, owing to the lower whole-body oxygen consumption in UCP1-de cient mice than in wild-type mice, particularly during the eating period [10]. Consistent with these previous studies in small rodents, we [11,12] demonstrated in healthy humans that DIT is approximately 50% higher in participants with metabolically active BAT than in those without it, suggesting BAT's contribution to facultative DIT in humans [13]. Human BAT activation after meal intake is directly con rmed by PET/CT using [ 15 ] uoro-thiaheptadecanoic acid radiotracers [14].…”

“…The above-mentioned DIT was obtained for 6-10 hours after meal ingestion, whereas the DIT in our study was measured for 2 hours after meal ingestion. We [11,12] previously reported that DIT with a mixed meal containing 60% carbohydrate was approximately 8.6% when measured for 5 hours using a whole-room human calorimeter. In the present study, EE was measured for 2 hours using a respiratory gas analyzer connected to a ventilated food; thus, collecting a stable value for a longer time period was di cult, probably because of the increasing stress of repeated immobilization for the measurement.…”

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

“…Similarly, glucose uptake by murine BAT was shown to peak at the end of the light phase, approximately 3 hours before the start of the active period in both male and female mice ( 33 ). A very recent paper suggests that cold-induced thermogenesis in humans is higher in males with high BAT activity compared to males with low BAT activity as assessed by 18 F-FDG-PET/CT scans, but only in the morning ( 34 ). On the contrary, another recent study did not find a diurnal variation in cold-induced thermogenesis ( 35 ).…”

“…Yet, similar to our results with cold-induced thermogenesis, diet-induced thermogenesis (ie, the increase in metabolic rate after food intake, also associated to BAT activity ( 59 )) has been shown to be higher in the morning than in the evening ( 60-62 ). Moreover, in mice as well as humans, postprandial lipid excursions are lower and postprandial fatty acid oxidation is higher in the morning than in the evening ( 18 , 19 , 34 ). These studies show the potential of time-restricted feeding specifically with an early timeframe that is aligned with the circadian clock ( 63 , 64 ), suggesting that the same could be true when applying cold exposure to improve whole-body lipid metabolism.…”

Fluvastatin Reduces Glucose Tolerance in Healthy Young Individuals Independently of Cold Induced BAT Activity

“…In addition to parameters of glucose sensitivity, we determined DIT by indirect calorimetry. DIT has been described as a major function of BAT ( 54 – 56 ), although this has been contested ( 57 , 58 ). DIT was not influenced by fluvastatin.…”