Functional brown adipose tissue and sympathetic activity after cold exposure in humans with type 1 narcolepsy

Study objectives: To investigate the activity of brown adipose tissue (BAT) in type 1 narcolepsy patients during cold exposure using two separate scans of sympathetic and metabolic activity of BAT in order to evaluate whether orexin deficiency leads to altered non-shivering thermoregulation in narcolepsy.

Methods: Seven patients with type 1 narcolepsy and seven healthy controls underwent two consecutive scans after 2 h cold exposure: 123I-meta-iodo-benzyl-guanidine (123I-MIBG) single photon emission computed tomography and 18F-2-deoxy-glucose (18F-FDG) positron emission tomography and computed tomography to visualize sympathetic innervation and metabolic activity of BAT, respectively. Plasma levels of eight hormones regulating BAT activity were measured before and after 2 h in the cold.

Results: 18F-FDG-uptake and uptake of 123I-MIBG in BAT after 2 h cold exposure was observed in all individuals, but the activity of BAT was not significantly different between type 1 narcolepsy patients and healthy controls (p>0.05). Plasma levels of GLP-1 were higher in type 1 narcolepsy patients compared with controls (p<0.05), but not altered by cold adaptation in patients and controls (p>0.05). FGF21 concentrations decreased after 2 h cold exposure in both type 1 narcolepsy patients and healthy subjects (p<0.05).

Conclusions: Sympathetic and metabolic activity of BAT was observed after cold exposure in patients with type 1 narcolepsy. Increased GLP-1 in narcolepsy may suggest autonomic dysfunction with metabolic changes. We conclude that BAT is functional after cold exposure in spite of the loss of orexinergic neurons in narcolepsy.