The Drosophila E78 nuclear receptor regulates dietary triglyceride uptake and systemic lipid levels
| Autor: | Hyuck-Jin Nam, Sophia A. Praggastis, Geanette Lam, Carl S. Thummel, Michael A. Horner |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Mutant Receptors Cytoplasmic and Nuclear Biology Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Animals Drosophila Proteins Homeostasis Lipase Regulation of gene expression Base Sequence Triglyceride Lipid metabolism Metabolism Lipid Metabolism Dietary Fats Cell biology Intestines 030104 developmental biology Gene Expression Regulation Nuclear receptor chemistry biology.protein Drosophila Female lipids (amino acids peptides and proteins) Lipid digestion 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Dev Dyn |
| ISSN: | 1097-0177 1058-8388 |
| DOI: | 10.1002/dvdy.287 |
| Popis: | Background Lipid levels are maintained by balancing lipid uptake, synthesis, and mobilization. Although many studies have focused on the control of lipid synthesis and mobilization, less is known about the regulation of lipid digestion and uptake. Results Here we show that the Drosophila E78A nuclear receptor plays a central role in intestinal lipid homeostasis through regulation of the CG17192 digestive lipase. E78A mutant adults fail to maintain proper systemic lipid levels following eclosion, with this effect largely restricted to the intestine. Transcriptional profiling by RNA-seq revealed a candidate gene for mediating this effect, encoding the predicted adult intestinal lipase CG17192. Intestine-specific disruption of CG17192 results in reduced lipid levels similar to that seen in E78A mutants. In addition, dietary supplementation with free fatty acids, or intestine-specific expression of either E78A or CG17192, is sufficient to restore lipid levels in E78A mutant adults. Conclusion These studies support the model that E78A is a central regulator of adult lipid homeostasis through its effects on CG17192 expression and lipid digestion. This work also provides new insights into the control of intestinal lipid uptake and demonstrate that nuclear receptors can play an important role in these pathways. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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