ArticlePLoS genetics2013
Identification of sphingolipid metabolites that induce obesity via misregulation of appetite, caloric intake and fat storage in Drosophila.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- No Influence of Overweight/Obesity on Exercise Lipid Oxidation: A Systematic Review.International journal of molecular sciences · 2020Pooled it
- Changes in Choline Metabolites and Ceramides in Response to a DASH-Style Diet in Older Adults.Nutrients · 2023Trial
- Sex-specific metabolic regulation by the Drosophila RNA-binding protein Nab2.bioRxiv : the preprint server for biology · 2026Article
- Exercise attenuates obesity-related cognitive and sleep-circadian dysfunctions by attenuating neuroinflammation via JAK/STAT in sex and age specific manner.International journal of obesity (2005) · 2026Article
- Time-restricted feeding promotes muscle function through purine cycle and AMPK signaling in Drosophila obesity models.Nature communications · 2023Article
- A Skeletal Muscle-Centric View on Time-Restricted Feeding and Obesity under Various Metabolic Challenges in Humans and Animals.International journal of molecular sciences · 2022Review
- The lymphatic vascular system: much more than just a sewer.Cell & bioscience · 2022Review
- The nutritional functions of dietary sphingomyelin and its applications in food.Frontiers in nutrition · 2022Review
- Plasma and vacuolar membrane sphingolipidomes: composition and insights on the role of main molecular species.Plant physiology · 2021Article
- Circulating Metabolites Associated with Postprandial Satiety in Overweight/Obese Participants: The SATIN Study.Nutrients · 2021Article
- Glycosphingolipids in Filamentous Fungi: Biological Roles and Potential Applications in Cosmetics and Health Foods.Frontiers in microbiology · 2021Review
- Systemic and heart autonomous effects of sphingosine Δ4 desaturase deficiency in lipotoxic cardiac pathophysiology.Disease models & mechanisms · 2020Article
- Time-restricted feeding restores muscle function in Drosophila models of obesity and circadian-rhythm disruption.Nature communications · 2019Article
- Single-Locus and Multi-Locus Genome-Wide Association Studies for Intramuscular Fat in Duroc Pigs.Frontiers in genetics · 2019Article
- Triacylglycerol Metabolism inGenetics · 2018Review
- Aging and Intermittent Fasting Impact on Transcriptional Regulation and Physiological Responses of Adult Drosophila Neuronal and Muscle Tissues.International journal of molecular sciences · 2018Article
- Ceramide-Protein Interactions Modulate Ceramide-Associated Lipotoxic Cardiomyopathy.Cell reports · 2018Article
- Specific skeletal muscle sphingolipid compounds in energy expenditure regulation and weight gain in Native Americans of Southwestern heritage.International journal of obesity (2005) · 2017Article
- Sphingolipids in obesity and related complications.Frontiers in bioscience (Landmark edition) · 2017Review
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Obesity is defined by excessive lipid accumulation. However, the active mechanistic roles that lipids play in its progression are not understood. Accumulation of ceramide, the metabolic hub of sphingolipid metabolism, has been associated with metabolic syndrome and obesity in humans and model systems. Here, we use Drosophila genetic manipulations to cause accumulation or depletion of ceramide and sphingosine-1-phosphate (S1P) intermediates. Sphingolipidomic profiles were characterized across mutants for various sphingolipid metabolic genes using liquid chromatography electrospray ionization tandem mass spectroscopy. Biochemical assays and microscopy were used to assess classic hallmarks of obesity including elevated fat stores, increased body weight, resistance to starvation induced death, increased adiposity, and fat cell hypertrophy. Multiple behavioral assays were used to assess appetite, caloric intake, meal size and meal frequency. Additionally, we utilized DNA microarrays to profile differential gene expression between these flies, which mapped to changes in lipid metabolic pathways. Our results show that accumulation of ceramides is sufficient to induce obesity phenotypes by two distinct mechanisms: 1) Dihydroceramide (C14:0) and ceramide diene (C14:2) accumulation lowered fat store mobilization by reducing adipokinetic hormone- producing cell functionality and 2) Modulating the S1P: ceramide (C14:1) ratio suppressed postprandial satiety via the hindgut-specific neuropeptide like receptor dNepYr, resulting in caloric intake-dependent obesity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.