ROLE OF HYPOTHALAMIC GENE EXPRESSION DURING CO-EXPOSURE TO SLEEP DISRUPTION AND A HIGH FAT DIET

Abstract

Background: Noise-induced sleep disruption (SD)contributes to obesity by increasingpalatable food intake. Altered genes in the hypothalamus maybe one mechanism linking the obese phenotype with co-exposure to SD plus palatable diets. The purpose was toinvestigatewhethergenes involved in regulating either sleep and weight gain alone were affected during chronic co-exposure to SD and a cafeteria-style dietin female rats.Methods: Three-month-old female Sprague-Dawley rats (N=20)previouslyfed a palatable diet (7d) were randomized to sleep ad libitumor noise-induced SD (8h/d,9d). Rats were continually fed the palatable diet. Heme regulated inhibitor (HRI), general control nonderepressible 2 (GCN2),trafficking kinesin-binding protein 2 (Trak2), myelin associated oligodendrocyte basic protein (Mobp), orexin-A (OXA), orexin 1 receptor (OX1R),estrogen receptor alpha (Esr1)and glyceraldehyde 3-phosphate dehydrogenase(gapdh)were measured by qPCR from the hypothalamus. Results: Sleepdisrupted females had less Esr1 (P=0.006),Trak2 (P=0.018)and OX1R (P=0.0504)mRNA,while HRI, GCN2,OXA andMobp mRNA were unaffected by co-exposure.Conclusion: Unlike male rats, apalatablediet alone may be sufficient to dysregulatethe eIF2ɑsignaling pathwayin female rats.Downregulation of hypothalamic orexin and estrogensignaling may contribute to weight gain during co-exposure to SD and a palatable diet in female rats.