Mechanisms underlying palmitic acid-induced disruption of locomotor activity and sleep behavior in Drosophila.

Comp Biochem Physiol C Toxicol Pharmacol

Department of Pediatric Neurology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, PR China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou 325000, PR China. Electronic address:

Published: February 2024

The globally prevalent of sleep disorders is partly attributed to unhealthy dietary habits. This study investigated the underlying mechanisms of elevated palmitic acid (PA) intake on locomotor activity and sleep behavior in Drosophila. Our results indicate that exposure to PA significantly elevated Drosophila's daytime and nighttime locomotor activity while concurrently reducing overall sleep duration. Utilizing 16S rRNA sequencing, we observed substantial alterations in the composition of the gut microbiota induced by PA, notably, characterized by a significant reduction in Lactobacillus plantarum. Furthermore, PA significantly increased the levels of inflammatory factors Upd3 and Eiger in Drosophila intestines, and downregulated the expression of Gad and Tph, as well as 5-HT1A. Conversely, Gdh and Hdc were significantly upregulated in the PA group. Supplementation with L. plantarum or lactic acid significantly ameliorated PA-induced disruptions in both locomotor activity and sleep behavior. This supplementation also suppressed the expression of intestinal inflammatory factors, thus restoring impaired neurotransmitter-mediated sleep-wake regulation. Moreover, specific knockdown of intestinal epithelial Upd3 or Eiger similarly restored disrupted neurotransmitter expression, ultimately improving PA-induced disturbances in Drosophila locomotor activity and sleep behavior. These findings provide important insights into the intricate interplay between dietary components and essential behaviors, highlighting potential avenues for addressing health challenges associated with modern dietary habits.

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http://dx.doi.org/10.1016/j.cbpc.2023.109813DOI Listing

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