A whole-organism screen identifies new regulators of fat storage

Lemieux, George A.; Liu, Jason; Mayer, Nasima; Bainton, Roland J.; Ashrafi, Kaveh; Werb, Zena

doi:10.1038/nchembio.534

Cited by 76 publications

(80 citation statements)

References 51 publications

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“…In preliminary experiments, we examined the effect of berberine, a known lipid modulator, by Nile Red staining 9,17) and confirmed that it has a lipid-reducing effect. We further validated the effect of berberine by Oil Red O stain, since it is a more accurate proxy for major fat stores in the subcellular compartments of the worm.…”

Section: Resultsmentioning

confidence: 90%

Screening of Isoquinoline Alkaloids for Potent Lipid Metabolism Modulation withCaenorhabditis elegans

Chow¹,

Sato²

2013

Bioscience, Biotechnology, and Biochemistry

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Section: Resultsmentioning

confidence: 90%

Screening of Isoquinoline Alkaloids for Potent Lipid Metabolism Modulation withCaenorhabditis elegans

Chow¹,

Sato²

2013

Bioscience, Biotechnology, and Biochemistry

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“…ImageJ (Schneider et al 2012) was used to quantify the fluorescence intensity of whole body, and the background signals were subtracted. For measuring the intestinal expression of fat-6p::fat-6::GFP or fat-7p::GFP, the first anterior intestinal cells were quantified as described previously (Lemieux et al 2011). …”

Section: Fluorescence Imagingmentioning

confidence: 99%

SREBP and MDT-15 protect C. elegans from glucose-induced accelerated aging by preventing accumulation of saturated fat

et al. 2015

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Glucose-rich diets shorten the life spans of various organisms. However, the metabolic processes involved in this phenomenon remain unknown. Here, we show that sterol regulatory element-binding protein (SREBP) and mediator-15 (MDT-15) prevent the life-shortening effects of a glucose-rich diet by regulating fat-converting processes in Caenorhabditis elegans. Up-regulation of the SREBP/MDT-15 transcription factor complex was necessary and sufficient for alleviating the life-shortening effect of a glucose-rich diet. Glucose feeding induced key enzymes that convert saturated fatty acids (SFAs) to unsaturated fatty acids (UFAs), which are regulated by SREBP and MDT-15. Furthermore, SREBP/MDT-15 reduced the levels of SFAs and moderated glucose toxicity on life span. Our study may help to develop strategies against elevated blood glucose and free fatty acids, which cause glucolipotoxicity in diabetic patients.

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“…For example, the Nile Red dye, which selectively stains lipid droplets, has been used in live C. elegans to identify genes (Ashrafi et al, 2003) or small molecules (Lemieux et al, 2011) that regulate fat storage. In another attempt to understand the basic biology of lipid droplets formation, a screen was carried out in human liver cells that were stained with a lipid droplet imaging kit to identify microRNAs (miRNAs) that regulate their accumulation (Whittaker et al, 2010).…”

Section: Lipid Labelingmentioning

confidence: 99%

Getting the whole picture: combining throughput with content in microscopy

Rimon

Schuldiner

2011

Journal of Cell Science

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Commentary 3743Introduction Technological developments in the past years have led to the emergence of high-throughput methods in cell biology (Box 1), where multiple perturbations of a system are automatically repeated in a controlled and identical fashion. These capabilities allow the acquisition of vast amounts of data on a biological system. Evaluating all aspects of such data using computational and mathematical tools can then lead to an unbiased systematic representation of the process studied (Ahn et al., 2006). Technical breakthroughs, often driven by the pharmaceutical industry, have pushed this field forwards and have led to major advances in drug screening (reviewed by Zanella et al., 2010) and numerous discoveries in basic biology.The need for systematic and unbiased approaches has always been at the core of scientific efforts. However, the technology that is required for such efforts often displays an inverse relationship between throughput (speed) and content (biological information). Sydney Brenner referred to this phenomenon by saying that highthroughput experiments are in danger of creating "low-input, high-throughput, no-output biology" (Brenner, 2008). Therefore, it remains a major goal to develop high-throughput science that will give all the advantages of being systematic, accurate, fast and unbiased without giving up the requirement to provide profound and highly informative data.Among the variety of high-throughput approaches available to date (Box 1), one of the methods that holds the promise to bridge the gap between these expectations is high-throughput microscopy, often also referred to as high-content screening (HCS). This is mainly owing to the ability of microscopy methods to focus on single cells at a subcellular resolution, in a time-dependent manner and to measure a large number of parameters in each frame. In this Commentary, we focus on the current frontiers of HCS by presenting the wide range of tools that are utilized and the biological questions that can be tackled using such approaches. We also discuss possible ways to increase content while maintaining throughput at all levels of the screen -from sample design and preparation through to the acquisition and analysis capabilities of the high-content imager system. The power of high-throughput microscopyHigh-throughput microscopy can be employed to address a wide spectrum of biological questions. At the basis of this capability lies the ever-growing variety of labeling methods (discussed below) that allow visualization of cellular architecture and function, as well as developmental or behavioral processes (Fig. 1). In addition, the technological advance of biological tools and microscopic platforms now enables screens to be performed in an array of genetic backgrounds, under different growth conditions and at various time points, as well as allowing the comparison of multiple tissues, cell lines or organisms. Combining the richness of visualization approaches with various experimental strategies creates nearly endless options ...

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A whole-organism screen identifies new regulators of fat storage

Cited by 76 publications

References 51 publications

Screening of Isoquinoline Alkaloids for Potent Lipid Metabolism Modulation withCaenorhabditis elegans

Screening of Isoquinoline Alkaloids for Potent Lipid Metabolism Modulation withCaenorhabditis elegans

SREBP and MDT-15 protect C. elegans from glucose-induced accelerated aging by preventing accumulation of saturated fat

Getting the whole picture: combining throughput with content in microscopy

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