Mutations in the carnitine palmitoyltransferase 1B (CPT1B) gene may be involved in the etiopathology of sleep disorders, increasing the risk of experiencing such disturbances in patients with this long chain fatty acid oxidation disorder (LCFAOD), according to a study recently published in Sleep.
“To elucidate the details of altered fatty acid metabolism, we determined levels of individual acylcarnitines and evaluated CPT1 activity in patients with [narcolepsy type 1 (NT1)] and other hypersomnia,” the authors wrote.
Patients with NT1 and other causes of hypersomnia showcased lower carnitine palmitoyltransferase (CPT) 1 activity than the control individuals. Further analysis confirmed that this enzymatic activity was an independent risk factor for the studied sleep disturbances.
To reach these results, the experimental study enrolled 108 patients with sleep disturbances, including NT1 and other hypersomnia entities in 57 and 51 cases, respectively.
Read more about LCFAOD etiology
The control group included 61 healthy individuals. Researchers assessed the CPT1 activity based on the C0/(t[C16]+t[C18]) ratio as well as 25 different acylcarnitines from the blood samples of all participants.
Moreover, to study the effect of fatty acid metabolism on NT1, 42 blood samples from patients with NT1 and healthy participants underwent transcriptome analysis to identify differences in gene expression. Interestingly, both the CPT2 and carnitine-acylcarnitine translocase (CACT) genes exhibited lower expression in patients with NT1.
Finally, addressing the increased risk of obesity among individuals with NT1, a clear association was found between the single nucleotide polymorphism rs5770917 of the CPT1B gene and obesity. Although there was no direct relation between the genetic variant and CPT1 activity, the activity of this enzyme was higher in participants with NT1 who were not obese and did not have the risk allele.
CPT1 activity could be a biomarker for screening sleep disorders such as NT1 and other hypersomnia, the Tokyo Metropolitan Institute of Medical Science said in a press release on the study.
Honda M, Shigematsu Y, Shimada M, Honda Y, Tokunaga K, Miyagawa T. Low carnitine palmitoyltransferase 1 activity is a risk factor for narcolepsy type 1 and other hypersomnia. Sleep. Published online July 10, 2022. doi:10.1093/sleep/zsac160
Abnormal fatty acid metabolism in narcolepsy type 1 and other hypersomnia. News release. Tokyo Metropolitan Institute of Medical Science; September 6, 2022.