The Drosophila estrogen-related receptor promotes triglyceride storage within the larval fat body.

IF 5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Journal of Lipid Research Pub Date : 2025-06-01 Epub Date: 2025-04-25 DOI:10.1016/j.jlr.2025.100815
Tess D Fasteen, Melody R Hernandez, Robert A Policastro, Maria C Sterrett, Gabriel E Zenter, Jason M Tennessen
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引用次数: 0

Abstract

The estrogen-related receptor (ERR) family of nuclear receptors serves key roles in coordinating triglyceride (TAG) accumulation with juvenile growth and development. In both insects and mammals, ERR activity promotes TAG storage during the postembryonic growth phase, with loss-of-function mutations in mouse Esrra and Drosophila melanogaster dERR inducing a lean phenotype. However, the role of insect ERRs in controlling TAG accumulation within adipose tissue remains poorly understood, as nearly all transcriptomic and metabolomic studies have relied on whole animal analyses. Here, we address this shortcoming by using tissue-specific approaches to examine the role of dERR in regulating lipid metabolism within the Drosophila larval fat body. We find that dERR autonomously promotes TAG accumulation within fat body cells and regulates expression of genes involved in glycolysis, β-oxidation, and isoprenoid metabolism. As an extension of these results, we not only discovered that dERR mutant fat bodies exhibit decreased expression of known dHNF4 target genes but also found that dHNF4 activity is decreased in dERR mutants. Overall, our findings indicate that dERR plays a multifaceted role in the larval fat body to coordinate lipid storage with carbohydrate metabolism and developmental growth.

果蝇雌激素相关受体促进甘油三酯在幼虫脂肪体内的储存。
雌激素相关受体(ERR)家族核受体(NRs)在协调甘油三酯(TAG)积累与幼鱼生长发育中起关键作用。在昆虫和哺乳动物中,ERR活性促进胚胎后生长阶段TAG的储存,小鼠Esrra和果蝇dERR中的功能缺失突变诱导瘦表型。然而,昆虫ERRs在控制脂肪组织中TAG积累中的作用仍然知之甚少,因为几乎所有的转录组学和代谢组学研究都依赖于全动物分析。在这里,我们通过使用组织特异性方法来研究dERR在果蝇幼虫脂肪体内调节脂质代谢中的作用,从而解决了这一缺点。我们发现dERR自主促进TAG在脂肪体细胞内的积累,并调节参与糖酵解、β-氧化和类异戊二烯代谢的基因的表达。作为这些结果的延伸,我们不仅发现dERR突变体脂肪体中已知dHNF4靶基因的表达降低,而且发现dERR突变体中dHNF4活性降低。总之,我们的研究结果表明,dERR在幼虫脂肪体中起着多方面的作用,协调脂肪储存与碳水化合物代谢和发育生长。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Lipid Research
Journal of Lipid Research 生物-生化与分子生物学
CiteScore
11.10
自引率
4.60%
发文量
146
审稿时长
41 days
期刊介绍: The Journal of Lipid Research (JLR) publishes original articles and reviews in the broadly defined area of biological lipids. We encourage the submission of manuscripts relating to lipids, including those addressing problems in biochemistry, molecular biology, structural biology, cell biology, genetics, molecular medicine, clinical medicine and metabolism. Major criteria for acceptance of articles are new insights into mechanisms of lipid function and metabolism and/or genes regulating lipid metabolism along with sound primary experimental data. Interpretation of the data is the authors’ responsibility, and speculation should be labeled as such. Manuscripts that provide new ways of purifying, identifying and quantifying lipids are invited for the Methods section of the Journal. JLR encourages contributions from investigators in all countries, but articles must be submitted in clear and concise English.
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