Unexpected Fat Distribution in Adolescents With Narcolepsy

Abstract

Narcolepsy type 1 is a chronic sleep disorder with significantly higher BMI reported in more than 50% of adolescent patients, putting them at a higher risk for metabolic syndrome in adulthood. Although well-documented, the body fat distribution and mechanisms behind weight gain in narcolepsy are still not fully understood but may be related to the loss of orexin associated with the disease. Orexin has been linked to the regulation of brown adipose tissue (BAT), a metabolically active fat involved in energy homeostasis. Previous studies have used BMI and waist circumference to characterize adipose tissue increases in narcolepsy but none have investigated its specific distribution. Here, we examine adipose tissue distribution in 19 adolescent patients with narcolepsy type 1 and compare them to 17 of their healthy peers using full body magnetic resonance imaging (MRI). In line with previous findings we saw that the narcolepsy patients had more overall fat than the healthy controls, but contrary to our expectations there were no group differences in supraclavicular BAT, suggesting that orexin may have no effect at all on BAT, at least under thermoneutral conditions. Also, in line with previous reports, we observed that patients had more total abdominal adipose tissue (TAAT), however, we found that they had a lower ratio between visceral adipose tissue (VAT) and TAAT indicating a relative increase of subcutaneous abdominal adipose tissue (ASAT). This relationship between VAT and ASAT has been associated with a lower risk for metabolic disease. We conclude that while weight gain in adolescents with narcolepsy matches that of central obesity, the lower VAT ratio may suggest a lower risk of developing metabolic disease.

Keywords: BMI; brown adipose tissue; hypocretin; magnetic resonance imaging (MRI); obesity; orexin; subcutaneous adipose tissue; visceral adipose tissue.

Figure 1

Illustration of body-composition. Merged and calibrated water-fat MRI images. The anterior and posterior thigh definitions are shown in the water image and visceral and subcutaneous adipose tissue definitions in the fat images. Intra muscular adipose tissue was defined as the average fat fraction of the anterior thighs.

Figure 2

Representative sBAT segmentation. The axial water, fat and fat fraction images shows a cross section of the supraclavicular BAT segmentation. The area circled in red (fat and water images) or black (fat fraction image) was defined as sBAT.

Figure 3

Results adipose tissue measures. (A) No difference in sBAT fat fraction between narcolepsy patients and healthy controls (p = 0.207). (B) Narcolepsy patients had more subcutaneous abdominal adipose tissue (ASAT). (C) Narcolepsy patients have more visceral adipose tissue (VAT) than controls. sBAT, supraclavicular brown adipose tissue; ASAT, abdominal subcutaneous adipose tissue; VAT, Visceral adipose tissue. ^*p < 0.05.

Figure 4

Visceral adipose tissue ratio. We found a lower ratio between VAT and VAT+ASAT (VATR) in narcolepsy patients. VAT, Visceral adipose tissue; VATR, visceral adipose tissue ratio, VAT/VAT+ASAT; ASAT, abdominal subcutaneous adipose tissue. ^*p < 0.05.