A Lipid Droplet-Associated GFP Reporter-Based Screen Identifies New Fat Storage Regulators in C. elegans

Liu, Zhenglong; Li, Xia; Ge, Qinlan; Ding, Mei; Huang, Xun

doi:10.1016/j.jgg.2014.03.002

Cited by 44 publications

(37 citation statements)

References 42 publications

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“…Overall, 14/37 strains, 38% showed changes in fat accumulation, much higher than the percentage of fat regulatory genes in the overall genome. For example, in a recent study 37/1600 genes (2.3%) were identified that affected lipid accumulation [46]. Thus, our functional studies demonstrate that lipid droplet associated proteins are enriched for essential proteins as well as proteins that influence fat accumulation in C. elegans .…”

Section: Resultsmentioning

confidence: 56%

Lipidomic and proteomic analysis of Caenorhabditis elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein

Vrablik

Petyuk

Larson

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Lipid droplets are cytoplasmic organelles that store neutral lipids for membrane synthesis and energy reserves. In this study, we characterized the lipid and protein composition of purified C. elegans lipid droplets. These lipid droplets are composed mainly of triacylglycerols, surrounded by a phospholipid monolayer composed primarily of phosphatidylcholine and phosphatidylethanolamine. The fatty acid composition of the triacylglycerols is rich in fatty acid species obtained from the dietary E. coli, including cyclopropane fatty acids and cis-vaccenic acid. Unlike other organisms, C. elegans lipid droplets contain very little cholesterol or cholesterol esters. Comparison of the lipid droplet proteomes of wild type and high-fat daf-2 mutant strains shows a very similar proteome in both strains, except that the most abundant protein in the C. elegans lipid droplet proteome, MDT-28, is relatively less abundant in lipid droplets isolated from daf-2 mutants. Functional analysis of lipid droplet proteins identified in our proteomic studies indicated an enrichment of proteins required for growth and fat homeostasis in C. elegans. Finally, we confirmed the localization of one of the newly identified lipid droplet proteins, ACS-4. We found that ACS-4 localizes to the surface of lipid droplets in the C. elegans intestine and skin. This study bolsters C. elegans as a model to study the dynamics and functions of lipid droplets in a multicellular organism.

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Section: Resultsmentioning

confidence: 56%

Lipidomic and proteomic analysis of Caenorhabditis elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein

Vrablik

Petyuk

Larson

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…To evaluate tissue-specific fat use, we used C. elegans strains in which lipid droplets were fluorescently labeled by Perilipin 1-GFP in a tissue-specific manner [50]. We measured lipid droplets in these strains via quantitative image analysis immediately after the swim, comparing exercised to non-exercise animals.…”

Section: Resultsmentioning

confidence: 99%

Single swim sessions in C. elegans induce key features of mammalian exercise

et al. 2017

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BackgroundExercise exerts remarkably powerful effects on metabolism and health, with anti-disease and anti-aging outcomes. Pharmacological manipulation of exercise benefit circuits might improve the health of the sedentary and the aging populations. Still, how exercised muscle signals to induce system-wide health improvement remains poorly understood. With a long-term interest in interventions that promote animal-wide health improvement, we sought to define exercise options for Caenorhabditis elegans.ResultsHere, we report on the impact of single swim sessions on C. elegans physiology. We used microcalorimetry to show that C. elegans swimming has a greater energy cost than crawling. Animals that swam continuously for 90 min specifically consumed muscle fat supplies and exhibited post-swim locomotory fatigue, with both muscle fat depletion and fatigue indicators recovering within 1 hour of exercise cessation. Quantitative polymerase chain reaction (qPCR) transcript analyses also suggested an increase in fat metabolism during the swim, followed by the downregulation of specific carbohydrate metabolism transcripts in the hours post-exercise. During a 90 min swim, muscle mitochondria matrix environments became more oxidized, as visualized by a localized mitochondrial reduction-oxidation-sensitive green fluorescent protein reporter. qPCR data supported specific transcriptional changes in oxidative stress defense genes during and immediately after a swim. Consistent with potential antioxidant defense induction, we found that a single swim session sufficed to confer protection against juglone-induced oxidative stress inflicted 4 hours post-exercise.ConclusionsIn addition to showing that even a single swim exercise bout confers physiological changes that increase robustness, our data reveal that acute swimming-induced changes share common features with some acute exercise responses reported in humans. Overall, our data validate an easily implemented swim experience as C. elegans exercise, setting the foundation for exploiting the experimental advantages of this model to genetically or pharmacologically identify the exercise-associated molecules and signaling pathways that confer system-wide health benefits.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-017-0368-4) contains supplementary material, which is available to authorized users.

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“…To observe LDs in worm neurons, we generated a neuron-specific GFP reporter line xdIs109 expressing the LD surface protein PLIN1. PLIN1::GFP forms ring-like structures when expressed in tissues with LDs (Bi, Xiang et al, 2012, Liu, Li et al, 2014. In xdIs109 animals, we mainly focused on the head region, which is the location of most neuronal soma.…”

Section: Lds Accumulate In Neurons Of Both Atgl-1 and Lid-1 Mutantsmentioning

confidence: 99%

Neuronal lipolysis participates in PUFA-mediated neural function and neurodegeneration

Yang

Liang

Lam

et al. 2020

Preprint

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Highlights:1. Neuronal lipolysis prevents LD accumulation in neurons.2. Defective neuronal lipolysis leads to touch sensation defect.3. Blocking neuronal lipolysis alleviates neurodegeneration. 4. Neuronal lipolysis and de novo PUFA biosynthesis have a synergistic effect in neurodegeneration. The incorporation of PUFAs into phospholipids promotes neurodegeneration. AbstractLipid droplets (LDs) are dynamic cytoplasmic organelles present in most eukaryotic cells. The appearance of LDs in neurons is not usually observed under physiological conditions, but is associated with neural diseases. It remains unclear how LD dynamics is regulated in neurons and how the appearance of LDs affects neuronal functions. We discovered that mutations of two key lipolysis genes atgl-1 and lid-1 lead to LD appearance in neurons of Caenorhabditis elegans. This neuronal lipid accumulation protects neurons from hyperactivation-triggered neurodegeneration, with a mild decrease in touch sensation. We also discovered that reduced biosynthesis of polyunsaturated fatty acids (PUFAs) causes similar effects, synergistically with decreased lipolysis.Furthermore, we demonstrated that these changes in lipolysis and PUFA biosynthesis increase PUFA partitioning toward triacylglycerol, and reduced incorporation of PUFAs into phospholipids increases neuronal protection. Together, these results suggest the crucial role of neuronal lipolysis in regulating neural functions and neurodegeneration cell-autonomously.

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A Lipid Droplet-Associated GFP Reporter-Based Screen Identifies New Fat Storage Regulators in C. elegans

Cited by 44 publications

References 42 publications

Lipidomic and proteomic analysis of Caenorhabditis elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein

Lipidomic and proteomic analysis of Caenorhabditis elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein

Single swim sessions in C. elegans induce key features of mammalian exercise

Neuronal lipolysis participates in PUFA-mediated neural function and neurodegeneration

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