Brown Adipose Tissue Energy Metabolism in Humans

Abstract

The demonstration of metabolically active brown adipose tissue (BAT) in humans primarily using positron emission tomography coupled to computed tomography (PET/CT) with the glucose tracer 18-fluorodeoxyglucose (18FDG) has renewed the interest of the scientific and medical community in the possible role of BAT as a target for the prevention and treatment of obesity and type 2 diabetes (T2D). Here, we offer a comprehensive review of BAT energy metabolism in humans. Considerable advances in methods to measure BAT energy metabolism, including nonesterified fatty acids (NEFA), chylomicron-triglycerides (TG), oxygen, Krebs cycle rate, and intracellular TG have led to very good quantification of energy substrate metabolism per volume of active BAT in vivo. These studies have also shown that intracellular TG are likely the primary energy source of BAT upon activation by cold. Current estimates of BAT's contribution to energy expenditure range at the lower end of what would be potentially clinically relevant if chronically sustained. Yet, 18FDG PET/CT remains the gold-standard defining method to quantify total BAT volume of activity, used to calculate BAT's total energy expenditure. Unfortunately, BAT glucose metabolism better reflects BAT's insulin sensitivity and blood flow. It is now clear that most glucose taken up by BAT does not fuel mitochondrial oxidative metabolism and that BAT glucose uptake can therefore be disconnected from thermogenesis. Furthermore, BAT thermogenesis is efficiently recruited upon repeated cold exposure, doubling to tripling its total oxidative capacity, with reciprocal reduction of muscle thermogenesis. Recent data suggest that total BAT volume may be much larger than the typically observed 50–150 ml with 18FDG PET/CT. Therefore, the current estimates of total BAT thermogenesis, largely relying on total BAT volume using 18FDG PET/CT, may underestimate the true contribution of BAT to total energy expenditure. Quantification of the contribution of BAT to energy expenditure begs for the development of more integrated whole body in vivo methods.

Sexual Dimorphisms in Adult Human Brown Adipose Tissue

“…We used 18 F‐FDG uptake for BAT quantification, which does not account for fatty acid consumption . Repeated cold exposures can increase BAT 18 F‐FDG uptake . We mitigated this effect by randomizing ambient temperature order.…”

Brown adipose tissue and glucose homeostasis – the link between climate change and the global rise in obesity and diabetes

“…It is therefore highly likely that current calculations suggesting only 1% of total daily glucose utilisation is partitioned across brown fat are inaccurate. 13 The total contribution of brown fat should therefore be revised due to the following:…”

“…It is based on calculated estimates of glucose oxidation in adult humans as determined in the cold (e.g. 13 ) or after feeding (e.g. 40 ).…”

“…12 Consequently the extent to which environmentally induced changes in brown fat function can impact on glucose homeostasis remains a matter of debate. 13 It should be noted that with repeated PET-CT scans on the same subject then brown fat is identifiable in most, if not all, adults, 14 and comparable quantification of brown fat has been shown between PET-CT and thermal imaging. 15 Consequently, it is likely that brown fat is present in all adults, 16 and as shown in rodents its temperature fluctuates appreciably over a 24h period.…”

Secretin Links Brown Fat to Food Intake: New Perspectives for Targeting Energy Balance in Humans

“…In the positive case, this would require that increased brown fat thermogenesis is not fully compensated by increasing food intake . Ten years ago, landmark publications reported on the presence of cold‐inducible brown fat in human adults . Cold‐inducible activation of human brown fat is impaired with age and in people with obesity and type 2 diabetes, whereas cold acclimation initiates remission in association with improved metabolic homeostasis.…”