Lipid and Carbohydrate Metabolism in Caenorhabditis elegans

Watts, Jennifer L.; Ristow, Michael

doi:10.1534/genetics.117.300106

Cited by 145 publications

(62 citation statements)

References 345 publications

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“…Our LC-MS results indicated that cyclopropane FA levels are undetectable in DA bacteria (Figure 1G). Since C. elegans are unable to synthesize cyclopropane FAs and rely on dietary sources for these compounds 62,63 , DA-fed worms have a lower abundance of cyclopropane FAs, in addition to reduced levels of most PUFAs, compared to OP-fed worms (Figure 1F). We therefore speculate that the decreased targeting of SEIP-1 to peri-LD cages in DA-fed worms may be partly explained by the lower levels of cyclopropane FAs and PUFAs.…”

Section: Discussionmentioning

confidence: 99%

“…We therefore speculate that the decreased targeting of SEIP-1 to peri-LD cages in DA-fed worms may be partly explained by the lower levels of cyclopropane FAs and PUFAs. Further, C. elegans use cyclopropane FAs for a substantial portion of the TAGs they produce 63 . It is therefore possible that lower levels of cyclopropane FAs in DA-fed worms may also impede TAG synthesis, resulting in overall reduced lipid content (Figure 1A, B).…”

Section: Discussionmentioning

confidence: 99%

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Dietary bacteria controlC. elegansfat content through pathways converging at phosphatidylcholine

Han,

Nien,

Jiang

et al. 2024

Preprint

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Dietary factors play a pivotal role in regulating metabolism in both health and disease. Lipid metabolism is particularly important for organismal health and longevity. However, the mechanisms by which dietary factors influence lipid metabolism remain poorly understood. Here, using the nematodeC. elegansas a model system, we investigated the influence of distinct bacterial diets on fat metabolism. We found that dietary vitamin B12 activates the S-adenosyl methionine (SAM) and phosphatidylcholine (PC) biosynthetic pathways. This activation leads to elevated levels of PC, which in turn suppresses the expression of the genefat-7and modulates lipid droplet dynamics through the regulatory proteins SBP-1/SREBP1 and SEIP-1/SEIPIN, respectively. Additionally, we identified a feedback loop involving SBP-1-mediated regulation of acid sphingomyelinase ASM-3, which enhances the production of phospho-choline and further stimulates PC synthesis. Our localization studies further suggest that ASM-3 may act as a signaling mediator between the intestine and coelomocytes, coordinating their roles in vitamin B12-mediated fat regulation. Overall, our findings shed new light on the complex interplay between diet and metabolic regulation, with a particular emphasis on the central role of phosphatidylcholine.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dietary bacteria controlC. elegansfat content through pathways converging at phosphatidylcholine

Han,

Nien,

Jiang

et al. 2024

Preprint

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“…Mutations in transition zone components like NPHP4 cause human ciliopathies 35 , suggesting that EV defects may contribute to ciliopathies such as nephronophthisis and polycystic kidney disease 4 . TTM-5 is a dihydroceramide desaturase (DEGS1/2) ortholog, which acts in a ceramide biosynthesis pathway to convert dihydroceramide to ceramide 22 . Ceramide is a bioactive signaling lipid that plays roles in ciliogenesis, ciliary TGF-β receptor/sonic hedgehog signaling, and exosome biogenesis 2,19 .…”

Section: Dihydroceramide Desaturase Ttm-5 Is Required For the Extende...mentioning

confidence: 99%

Ciliary intrinsic mechanisms regulate dynamic ciliary extracellular vesicle release from sensory neurons

Wang,

Saul,

Nikonorova

et al. 2023

Preprint

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SummaryCilia-derived extracellular vesicles (EVs) contain signaling proteins and act in intercellular communication. Polycystin-2 (PKD-2), a transient receptor potential channel, is a conserved ciliary EVs cargo.Caenorhabditis elegansserves as a model for studying ciliary EV biogenesis and function.C. elegansmales release EVs in a mechanically-induced manner and deposit PKD-2-labeled EVs onto the hermaphrodite vulva during mating, suggesting an active release process. Here, we study the dynamics of ciliary EV release using time-lapse imaging and find that cilia can sustain the release of PKD-2-labeled EVs for a two-hour duration. Intriguingly, this extended release doesn’t require neuronal synaptic transmission. Instead, ciliary intrinsic mechanisms regulate PKD-2 ciliary membrane replenishment and dynamic EV release. The ciliary kinesin-3 motor KLP-6 is necessary for both initial and extended ciliary EV release, while the transition zone protein NPHP-4 is required only for sustained EV release. The dihydroceramide desaturase DEGS1/2 ortholog TTM-5 is highly expressed in the EV-releasing sensory neurons, localizes to cilia, and is required for sustained but not initial ciliary EV release, implicating ceramide in ciliary ectocytosis. The study offers a comprehensive portrait of real-time ciliary EV release, and mechanisms supporting cilia as proficient EV release platforms.

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“…β-branched fatty acids are highly unusual because they cannot be obtained via canonical fatty acid biosynthesis from acetate or propionate, nor from leucine-derived monomethyl branched chain fatty acids which contain a methyl branch at the terminal carbon (Fig. 4A) 39,56,57 . We therefore hypothesized that the unusual β-methyl group is installed by an S-adenosyl methionine (SAM)-dependent methyltransferase.…”

Section: A Methyltransferase Conserved Across Nematodamentioning

confidence: 99%

Evolutionarily related host and microbial pathways regulate fat desaturation

Fox,

Helf,

Burkhardt

et al. 2023

Preprint

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Fatty acid desaturation is central to metazoan lipid metabolism and provides building blocks of membrane lipids and precursors of diverse signaling molecules. Nutritional conditions and associated microbiota regulate desaturase expression, but the underlying mechanisms have remained unclear. Here, we show that endogenous and microbiota-dependent small molecule signals promote lipid desaturation via the nuclear receptor NHR-49/PPARα in C. elegans. Untargeted metabolomics of a β-oxidation mutant, acdh-11, in which expression of the stearoyl-CoA desaturase FAT-7/SCD1 is constitutively increased, revealed accumulation of a β-cyclopropyl fatty acid, becyp#1, that potently activates fat-7 expression via NHR-49. Biosynthesis of becyp#1 is strictly dependent on expression of cyclopropane synthase by associated bacteria, e.g., E. coli. Screening for structurally related endogenous metabolites revealed a β-methyl fatty acid, bemeth#1, whose activity mimics that of microbiota-dependent becyp#1, but is derived from a methyltransferase, fcmt-1, that is conserved across Nematoda and likely originates from bacterial cyclopropane synthase via ancient horizontal gene transfer. Activation of fat-7 expression by these structurally similar metabolites is controlled by distinct mechanisms, as microbiota-dependent becyp#1 is metabolized by a dedicated β-oxidation pathway, while the endogenous bemeth#1 is metabolized via α-oxidation. Collectively, we demonstrate that evolutionarily related biosynthetic pathways in metazoan host and associated microbiota converge on NHR-49/PPARα to regulate fat desaturation.

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Lipid and Carbohydrate Metabolism in Caenorhabditis elegans

Cited by 145 publications

References 345 publications

Dietary bacteria controlC. elegansfat content through pathways converging at phosphatidylcholine

Dietary bacteria controlC. elegansfat content through pathways converging at phosphatidylcholine

Ciliary intrinsic mechanisms regulate dynamic ciliary extracellular vesicle release from sensory neurons

Evolutionarily related host and microbial pathways regulate fat desaturation

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