The impact of fat-body-specific Neurexin-1-knockdown in Drosophila melanogaster and its role in metabolism and eating behaviour

Background: Genetic variants in human neurexin-3 (NRXN3) have been linked to body fat distribution metrics, such as waist-to-hip-ratio ([1]). Neurexin1-null flies present a significantly altered metabolic profile characterized by decreased lipid and carbohydrate stores ([2]). In this study, we examined whether Nrx-1 plays a role in regulating food intake and body weight in Drosophila melanogaster.

Methods: Due to the high conservation of glucose and fat metabolism pathways between fruit flies and humans, Drosophila melanogaster serves as an excellent model to study physiological parallels. Using the GAL4-UAS system, we created an adipose tissue-specific knockdown (KD) of Nrx-1 (the fly homologue of the human NRXN3) by crossing a UAS-Nrx-1 line with a tissue-specific driver line. We then investigated its localized effect on adipocytes and its influence on whole-body metabolic processes. In addition, we assessed whether the KD of Nrx-1 in the fat body alters the food intake of the flies.

Results and conclusion: The downregulation of Nrx-1 appears to affect the metabolic phenotypes, as we observed a significant reduction in body weight in both KD-flies and larvae, despite no detectable changes in food intake. Ongoing analyses aim to further explore metabolic processes, including triglycerides and glycogen storage, to gain more insights into the underlying mechanisms behind the observed body weight alterations.

Publication History

Article published online:
28 May 2025

• Literatur

• 1 Heard-Costa NL, Zillikens MC, Monda KL, Johansson A, Harris TB, Fu M. et al. NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium. PLoS Genet 2009; 5: e1000539
• 2 Levy KA, Weisz ED, Jongens TA.. Loss of neurexin-1 in Drosophila melanogaster results in altered energy metabolism and increased seizure susceptibility. Hum Mol Genet 2022; 31: 3422-38