[HTML][HTML] β3-Adrenergically induced glucose uptake in brown adipose tissue is independent of UCP1 presence or activity: mediation through the mTOR pathway
JM Olsen, RI Csikasz, N Dehvari, L Lu, A Sandström… - Molecular …, 2017 - Elsevier
JM Olsen, RI Csikasz, N Dehvari, L Lu, A Sandström, AI Öberg, J Nedergaard…
Molecular metabolism, 2017•ElsevierObjective Today, the presence and activity of brown adipose tissue (BAT) in adult humans is
generally equated with the induced accumulation of [2-18 F] 2-fluoro-2-deoxy-d-glucose ([18
F] FDG) in adipose tissues, as investigated by positron emission tomography (PET)
scanning. In reality, PET-FDG is currently the only method available for in vivo quantification
of BAT activity in adult humans. The underlying assumption is that the glucose uptake
reflects the thermogenic activity of the tissue. Methods To examine this basic assumption, we …
generally equated with the induced accumulation of [2-18 F] 2-fluoro-2-deoxy-d-glucose ([18
F] FDG) in adipose tissues, as investigated by positron emission tomography (PET)
scanning. In reality, PET-FDG is currently the only method available for in vivo quantification
of BAT activity in adult humans. The underlying assumption is that the glucose uptake
reflects the thermogenic activity of the tissue. Methods To examine this basic assumption, we …
Objective
Today, the presence and activity of brown adipose tissue (BAT) in adult humans is generally equated with the induced accumulation of [2-18F]2-fluoro-2-deoxy-d-glucose ([18F]FDG) in adipose tissues, as investigated by positron emission tomography (PET) scanning. In reality, PET-FDG is currently the only method available for in vivo quantification of BAT activity in adult humans. The underlying assumption is that the glucose uptake reflects the thermogenic activity of the tissue.
Methods
To examine this basic assumption, we here followed [18F]FDG uptake by PET and by tissue [3H]-2-deoxy-d-glucose uptake in wildtype and UCP1(−/−) mice, i.e. in mice that do or do not possess the unique thermogenic and calorie-consuming ability of BAT.
Results
Unexpectedly, we found that β3-adrenergically induced (by CL-316,243) glucose uptake was UCP1-independent. Thus, whereas PET-FDG scans adequately reflect glucose uptake, this acute glucose uptake is not secondary to thermogenesis but is governed by an independent cellular signalling, here demonstrated to be mediated via the previously described KU-0063794-sensitive mTOR pathway.
Conclusions
Thus, PET-FDG scans do not exclusively reveal active BAT deposits but rather any tissue possessing an adrenergically-mediated glucose uptake pathway. In contrast, we found that the marked glucose uptake-ameliorating effect of prolonged β3-adrenergic treatment was UCP1 dependent. Thus, therapeutically, UCP1 activity is required for any anti-diabetic effect of BAT activation.
Elsevier