Good quality sleep is of the highest importance for our day-to-day functioning and overall health. A new study published in Science Advances describes a potential link between omega-3 fatty acid and proper functioning of the FABP7 protein in the regulation of sleep cycles.
The phenomenon of sleep occurs through the animal kingdom, suggesting that it plays an important and conserved role. Despite this, only few mechanisms governing sleep across species have been described and linked to neuronal signaling, immune functions and genetic factors. Recently, a group of cells – named astrocytes, have been found to play a role in sleep regulation. These cells express a gene that encodes FABP7 protein. When FABP7 is overexpressed in the brains of mice it causes an increase in total sleep time.
FABP7 belongs to a group of conserved FABP proteins, which are associated with metabolic, inflammatory and energy homeostasis pathways. All FABP proteins share conserved structural domains and have a strong affinity to bind fatty acids. Upon binding with omega-3 fatty acid, FABP7 protein changes its conformation and exposes a nuclear localization sequence which allows FABP to be inside the nucleus. Study published by Jason Gerstner and team in Science Advances describes the effect of mutated FABP7 on sleep in humans, mice and fruit flies. Researchers found an association between one mutation in FABP7 protein and fragmented sleep in humans.
The study evaluated 294 adult males during 7 day period using actigraphy (non-invasive method for monitoring rest/activity cycles) and analyzed DNA sequences encoding FABP7.
29 of the 294 subjects were identified as carriers of a single point mutation at position 61 of the FABP7 protein (Fabp7T61M). This mutation affected FABP7 binding to omega-3 fatty acids, and as result FABP7’s ability to expose its nuclear localization sequence.
Sleep assessment of the individuals didn’t show difference in total sleep time; however, carriers of the mutation had abnormally fragmented sleep with no other significant differences in age, body mass or overall health. Researchers observed the same sleeping pattern in genetically modified mice lacking the Fabp7 gene. These mice experienced periods of REM (rapid eyes movement) sleep more frequency and woke up more often than wildtype mice (mice without the Fabp7 deletion).
To address whether involvement of Fabp7 gene is conserved in sleep regulation beyond vertebrates, the wild type and point mutation Fabp7 gene were expressed in fruit flies. Flies carrying the mutated version showed decreased sleep time over 24h period and increased sleep fragmentation compared to wild type.
Together these results indicate that the Fabp7. T61M mutation causes sleep fragmentation and this feature is conserved across the animal kingdom. The exact function of Fabp7 gene is not yet fully understood; however, this research implies that nuclear localization sequence, which is disrupted in the mutant is important and possibly nuclear Fabp7 activates more genes involved in sleeping regulation. Since the nuclear localization sequence is exposed following Fabp7 binding to omega 3 fatty acid, this research demonstrates a link between high fatty-acid diet and sleep regulation across species.
Written By: Bella Groisman, PhD