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Unexpected Fat Distribution in Adolescents With Narcolepsy
Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV). AMRA Med AB, Linkoping, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Uppsala Univ, Sweden.
Univ Gothenburg, Sweden.
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2018 (English)In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 9, article id 728Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA , 2018. Vol. 9, article id 728
Keywords [en]
orexin; hypocretin; brown adipose tissue; visceral adipose tissue; subcutaneous adipose tissue; BMI; magnetic resonance imaging (MRI); obesity
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:liu:diva-153502DOI: 10.3389/fendo.2018.00728ISI: 000452268600001OAI: oai:DiVA.org:liu-153502DiVA, id: diva2:1274647
Note

Funding Agencies|Research Council of South East Sweden [FORSS-480551]; Knut and Alice Wallenberg foundation [KAW 2013.0076]

Available from: 2019-01-02 Created: 2019-01-02 Last updated: 2019-01-04
In thesis
1. Brain Networks and Dynamics in Narcolepsy
Open this publication in new window or tab >>Brain Networks and Dynamics in Narcolepsy
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Narcolepsy is a chronic sleep disorder, characterised by excessive daytime sleepiness with frequent uncontrollable sleep attacks. In addition to sleeprelated problems, changes in cognition have also been observed in patients with narcolepsy and has been linked to the loss of Orexin-A in a number of studies. Results from previous functional and structural neuroimaging studies would suggest that the loss of Orexin-A has numerous downstream effects in terms of both resting state glucose metabolism and perfusion and reduction in cortical grey matter.

Specifically, studies investigating narcolepsy with positron emission tomography (PET) and single photon emission computed tomography (SPECT) have observed aberrant perfusion and glucose metabolism in the hypothalamus and thalamus, as well as in prefrontal cortex. A very recent PET study in a large cohort of adolescents with type 1 narcolepsy further observed that the hypoand hypermetabolism in many of these cortico-frontal and subcortical brain regions also exhibited significant correlations with performance on a number of neurocognitive tests. These findings parallel those found in structural neuroimaging studies, where a reduction of cortical grey matter in frontotemporal areas has been observed.

The Aim of this thesis was to investigate mechanisms and aetiology behind the symptoms in narcolepsy through the application of different neuroimaging techniques. I present in this thesis evidence supporting that the complaints about subjective memory deficits in narcolepsy are related to a misallocation of resources.

I further describe how this has its seat in defective default mode network activation, possibly involving alterations to GABA and Glutamate signaling. In addition to this, I present our findings of a structural deviation in an area of the brainstem previously not described in the aetiology of narcolepsy.

This finding may have implications for further understanding the aetiology of the disease and the specific neuronal populations involved.

In addition to this, I show evidence from adipose tissue measurements in specific compartments, confirming that weight gain in narcolepsy is characterized by centrally located weight gain and may be specifically related to OX changes, but maybe not brown adipose tissue volume.

The findings presented in this thesis provides new insights to the pathophysiology of narcolepsy beyond the well-known depletion of OX producing neurons in the hypothalamus.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2018. p. 54
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1651
National Category
Neurosciences Radiology, Nuclear Medicine and Medical Imaging Neurology Physiology
Identifiers
urn:nbn:se:liu:diva-153629 (URN)10.3384/diss.diva-153629 (DOI)9789176851814 (ISBN)
Public defence
2019-01-25, Hugo Theorells sal, Campus US, Linköping, 09:15 (English)
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Available from: 2019-01-04 Created: 2019-01-04 Last updated: 2019-01-07Bibliographically approved

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