Dataset Information

Drosophila Lipase 3 Mediates the Metabolic Response to Starvation and Aging.

ABSTRACT: The human LIPA gene encodes for the enzyme lysosomal acid lipase, which hydrolyzes cholesteryl ester and triacylglycerol. Lysosomal acid lipase deficiency results in Wolman disease and cholesteryl ester storage disease. The Drosophila genome encodes for two LIPA orthologs, Magro and Lipase 3. Magro is a gut lipase that hydrolyzes triacylglycerides, while Lipase 3 lacks characterization based on mutant phenotypes. We found previously that Lipase 3 transcription is highly induced in mutants with defects in peroxisome biogenesis, but the conditions that allow a similar induction in wildtypic flies are not known. Here we show that Lipase 3 is drastically upregulated in starved larvae and starved female flies, as well as in aged male flies. We generated a lipase 3 mutant that shows sex-specific starvation resistance and a trend to lifespan extension. Using lipidomics, we demonstrate that Lipase 3 mutants accumulate phosphatidylinositol, but neither triacylglycerol nor diacylglycerol. Our study suggests that, in contrast to its mammalian homolog LIPA, Lipase 3 is a putative phospholipase that is upregulated under extreme conditions like prolonged nutrient deprivation and aging.

SUBMITTER: Hanschke L

PROVIDER: S-EPMC9261307 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Drosophila Lipase 3 Mediates the Metabolic Response to Starvation and Aging.

Hänschke Lea L Heier Christoph C Maya Palacios Santiago José SJ Özek Huseyin Erdem HE Thiele Christoph C Bauer Reinhard R Kühnlein Ronald P RP Bülow Margret H MH

Frontiers in aging 20220214

The human LIPA gene encodes for the enzyme lysosomal acid lipase, which hydrolyzes cholesteryl ester and triacylglycerol. Lysosomal acid lipase deficiency results in Wolman disease and cholesteryl ester storage disease. The Drosophila genome encodes for two LIPA orthologs, Magro and Lipase 3. Magro is a gut lipase that hydrolyzes triacylglycerides, while Lipase 3 lacks characterization based on mutant phenotypes. We found previously that Lipase 3 transcription is highly indu ...[more]

PMID: 35821816

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Project description:Background All animals must be able to adapt to changes in nutrient quality and supply. One striking aspect of this adaptive response is the extension of lifespan when caloric intake is reduced. These animals are also more resistant to various stresses, including starvation. We have characterized the response of adult Drosophila males and females to starvation and sugar conditions using high density microarrays. Results We have organized the regulated genes into specific metabolic and physiologic pathways. Most of the highly regulated genes have a strong sex bias. In addition to expected sex specific changes, such as egg production in females, we found unexpected biases in sensory systems, amino acid and purine metabolism, and signaling pathways. Comparison of starvation to caloric restriction revealed numerous overlaps. Conclusions Our results support the notion that starvation response shares similarities to caloric restriction. They have relevance for sex specific differences in longevity and in response to nutrient conditions which alter lifespan. Nutrient Conditions and Fly handling Larvae were kept on apple juice agar plates with yeast, and the larvae were raised at 25°C. For the developmental control larvae were collected 39-41 h AEL, for the developmental time-points at 51-53 hours and every 12 hours until 99-101 hours. Adult flies were kept at 25°C in 50 ml PS-tubes flat bottom (Greiner bio-one, Frickenhausen, Germany) on standard fly food (16.5 g yeast, 81,5 g cornmeal, 8 g agar, 100 ml sugar beet sirup and 200 ml 10% Nipagin in EtOH). Flies were collected that had hatched in 24 hours and kept in groups of ~200 flies/tube. After 5 days we separated males and females and put them in groups of 80/28 ml PS-tube. We allowed for one day CO2 recovery on standard fly food before flies were moved to 1) tubes with yeast paste on PBS soaked filter paper (control) 2) tubes with only PBS soaked filter paper (starvation) or 3) tubes with filter paper soaked in PBS with 20% Sucrose (sugar). After 24 or 48 hours flies were shock frozen in liquid nitrogen and stored at - 80°C for further handling. Males and females were assayed separately. For females, we performed 24 and 48 starvation, and 24 and 48 hours sugar. For the males only 24 hour starvation was done, since most died upon 48 hour starvation; and 24 and 48 hour sugar. Briefly, flies were collected within a 24 hour period, allowed to stay together for 4 days, separated into males and females, and allowed one day recovery in normal fly food. Afterwards, the flies were placed into three conditions: fresh yeast plus PBS, PBS or PBS plus 20 % sucrose. These experiments essentially parallel the experimental set up of previous larval experiments (7). The starvation and PBS were then compared with yeast (control). Keywords: ordered

Project description:Background All animals must be able to adapt to changes in nutrient quality and supply. One striking aspect of this adaptive response is the extension of lifespan when caloric intake is reduced. These animals are also more resistant to various stresses, including starvation. We have characterized the response of adult Drosophila males and females to starvation and sugar conditions using high density microarrays. Results We have organized the regulated genes into specific metabolic and physiologic pathways. Most of the highly regulated genes have a strong sex bias. In addition to expected sex specific changes, such as egg production in females, we found unexpected biases in sensory systems, amino acid and purine metabolism, and signaling pathways. Comparison of starvation to caloric restriction revealed numerous overlaps. Conclusions Our results support the notion that starvation response shares similarities to caloric restriction. They have relevance for sex specific differences in longevity and in response to nutrient conditions which alter lifespan. Nutrient Conditions and Fly handling Larvae were kept on apple juice agar plates with yeast, and the larvae were raised at 25Â°C. For the developmental control larvae were collected 39-41 h AEL, for the developmental time-points at 51-53 hours and every 12 hours until 99-101 hours. Adult flies were kept at 25Â°C in 50 ml PS-tubes flat bottom (Greiner bio-one, Frickenhausen, Germany) on standard fly food (16.5 g yeast, 81,5 g cornmeal, 8 g agar, 100 ml sugar beet sirup and 200 ml 10% Nipagin in EtOH). Flies were collected that had hatched in 24 hours and kept in groups of ~200 flies/tube. After 5 days we separated males and females and put them in groups of 80/28 ml PS-tube. We allowed for one day CO2 recovery on standard fly food before flies were moved to 1) tubes with yeast paste on PBS soaked filter paper (control) 2) tubes with only PBS soaked filter paper (starvation) or 3) tubes with filter paper soaked in PBS with 20% Sucrose (sugar). After 24 or 48 hours flies were shock frozen in liquid nitrogen and stored at - 80Â°C for further handling. Males and females were assayed separately. For females, we performed 24 and 48 starvation, and 24 and 48 hours sugar. For the males only 24 hour starvation was done, since most died upon 48 hour starvation; and 24 and 48 hour sugar. Briefly, flies were collected within a 24 hour period, allowed to stay together for 4 days, separated into males and females, and allowed one day recovery in normal fly food. Afterwards, the flies were placed into three conditions: fresh yeast plus PBS, PBS or PBS plus 20 % sucrose. These experiments essentially parallel the experimental set up of previous larval experiments (7). The starvation and PBS were then compared with yeast (control).

Dataset Information

Drosophila Lipase 3 Mediates the Metabolic Response to Starvation and Aging.

Publications

Drosophila Lipase 3 Mediates the Metabolic Response to Starvation and Aging.

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