788V Poster Online - Virtual Posters
Wednesday April 06, 4:00 PM - 7:00 PM

Authors:
Rajitha Udakara Sampath Hemba-Waduge ¹; Xiahe Huang ²; Mengmeng Liu ¹; Xiao Li ^1,3; Yingchun Wang ²; Jun-yuan Ji ¹

Affiliations:
1) Tulane University School of Medicine, New Orleans, LA; 2) Chinese Academy of Sciences, Beijing, China; 3) Princeton University, Princeton, NJ

Keywords:
b. metabolism; b. metabolism

Dysregulated Wnt signaling causes aberrant development and diseases such as cancer, but the role of Wnt signaling in regulating lipid metabolism remains poorly understood. We have reported that hyperactive Wnt signaling in Drosophila larvae reduces lipid accumulation in the fat body, which can be strongly rescued by feeding the larvae with proteasome inhibiting peptide boronic acids, such as Bortezomib. Interestingly, hyperactive Wnt signaling in adipocytes increases the levels of different types of free fatty acids but reduces the levels of a variety of triglycerides. To elucidate the mechanisms of how Wnt signaling regulates lipid homeostasis in adipocytes, we have performed transcriptomic and quantitative proteomic analyses using larvae with hyperactive Wnt signaling with or without Bortezomib treatment. These analyses led us to identify genes involved in regulation of lipid mobilization, such as PLIN1 (Perilipin1), PLIN2, and genes encoding factors that regulate fatty acid beta-oxidation. Both PLIN1 and PLIN2 are significantly reduced by hyperactive Wnt signaling, but these effects are strongly reversed by Bortezomib treatment. Our genetic analyses suggest that adipocyte defects caused by hyperactive Wnt signaling can be strongly enhanced by depleting PLIN1, but rescued by ectopic expression of PLIN1, PLIN2, or both. Taken together, these observations suggest that Wnt signaling may regulate lipid homeostasis by promoting lipid mobilization through regulating the expression of PLIN1 and PLIN2 in larval fat body.