Different Metabolic Responses of Human Brown Adipose Tissue to Activation by Cold and Insulin

Abstract

We investigated the metabolism of human brown adipose tissue (BAT) in healthy subjects by determining its cold-induced and insulin-stimulated glucose uptake and blood flow (perfusion) using positron emission tomography (PET) combined with computed tomography (CT). Second, we assessed gene expression in human BAT and white adipose tissue (WAT). Glucose uptake was induced 12-fold in BAT by cold, accompanied by doubling of perfusion. We found a positive association between whole-body energy expenditure and BAT perfusion. Insulin enhanced glucose uptake 5-fold in BAT independently of its perfusion, while the effect on WAT was weaker. The gene expression level of insulin-sensitive glucose transporter GLUT4 was also higher in BAT as compared to WAT. In conclusion, BAT appears to be differently activated by insulin and cold; in response to insulin, BAT displays high glucose uptake without increased perfusion, but when activated by cold, it dissipates energy in a perfusion-dependent manner.

Brown Adipose Tissue in Humans

“…Therefore 18 FDG is cleared from the plasma into muscles, its availability in plasma is decreased and 'counts' are lower in BAT. However, by modeling FDG uptake over time, we were able to demonstrate that insulin is a potent stimulator of BAT activity (Orava et al 2011). Only dynamic data analysis with input information gives reliable values of BAT activity for comparisons between groups or subjects in interventions.…”

“…HERE --Cold activation enhances hBAT perfusion significantly when studied using 15 O--H2O--PET (Orava et al 2011, Muzik et al 2012. Insulin stimulation during euglycemia increases BAT glucose uptake five--fold in line with whole body insulin sensitivity but without any increment in perfusion (Orava et al 2011). When Muzik and co--workers used 15 O2 to assess directly oxygen consumption during cold stimulation, MRO2 values were shown to increase (Muzik et al 2012).…”

“…PET is a highly sensitive and specific imaging tool for studies of BAT physiology (Table 1). (Orava et al 2011, Muzik et al 2012 [ (Virtanen et al 2009, Orava et al 2011 Free fatty acid metabolism (Ouellet et al 2012) [ 18 F]FTHA 109…”

“…Relative to FDG, this numerical value has been shown to approximate unity in skeletal muscle (Peltoniemi et al 2000), myocardium (Ng et al 1998) and adipose tissue (Virtanen et al 2001), and to hold constant across metabolic disease states. Therefore it has been assumed to be 1.0 also for human BAT (Virtanen 2009 (Iida et al, 1988, Ruotsalainen et 1997 and applied to the study of BAT as well (Orava et al 2011, Muzik et al 2012. Oxygen consumption may be determined directly in BAT using 15 O2--PET (Muzik et al 2012).…”

Brown adipose tissue: what have we learned since its recent identification in human adults

“…However, just two years later, with the publication of three articles in the same edition of the New England Journal of Medicine, the scientific community accepted that at least a fraction of human adults possess brown adipose tissue (12,13,14,35). We will review those articles shortly (Table 1).…”