MRNA-seq analysis of early adult C. elegans fatty acid synthesis mutant following extended L1 arrest
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA737503 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Early-life malnutrition increases adult disease risk in humans, but the causal changes in gene regulation, signaling, and metabolism are unclear. In the roundworm Caenorhabditis elegans, early-life starvation causes well-fed larvae to develop germline tumors and other gonad abnormalities as adults. Furthermore, reduced insulin/IGF signaling (IIS) during larval development suppresses these starvation-induced abnormalities. How early-life starvation and IIS affect adult pathology is unknown. We show that early-life starvation has pervasive effects on adult gene expression that are largely reversed by reduced IIS following recovery from starvation. Early-life starvation increases adult fatty-acid synthetase fasn-1 expression in daf-2 IIS receptor-dependent fashion, and fasn-1/FASN promotes starvation-induced abnormalities. Lipidomic analysis reveals increased levels of phosphatidylcholine in adults subjected to early-life starvation, and supplementation with unsaturated phosphatidylcholine during development suppresses starvation-induced abnormalities. Genetic analysis of fatty-acid desaturases reveals positive and negative effects of desaturation on development of starvation-induced abnormalities. In particular, the delta 3 fatty-acid desaturase fat-1 and the delta 5 fatty-acid desaturase fat-4 inhibit and promote development of abnormalities, respectively. fat-4 is epistatic to fat-1, suggesting that arachidonic acid, or lipids that contain it, promotes development of starvation-induced abnormalities. This work shows that early-life starvation and IIS converge on regulation of adult lipid metabolism, affecting stem-cell proliferation, tumor formation, and additional adult pathologies.
2022-11-08 | GSE178171 | GEO
Project description:We characterized the effects of early-life starvation and reduced insulin/insulin-like signaling (IIS) during larval development on adult gene expression using mRNA-seq of whole worms. In our two-factor design, 'starved' worms were cultured without food (E. coli) in L1 arrest for eight days, and 'control' worms were starved overnight for synchronization. Both populations of worms were fed ad libitum with either empty vector (EV; negative control) or daf-2/InsR RNAi food (reduced IIS). RNAi was used rather than a daf-2 mutant so that the results would not be confounded by daf-2 function during L1 arrest, instead disrupting daf-2 only after starvation in fed, developing larvae. Upon reaching adulthood, animals were collected for transcript profiling.
2022-11-08 | GSE178170 | GEO
Project description:mRNA-seq analysis of early adult C. elegans following extended L1 arrest with reduced insulin/insulin-like signaling
| PRJNA737502 | ENA
Project description:Medium chain fatty acid (MCFAs) synthesis Metagenome
| PRJNA950190 | ENA
Project description:We report the gene expression in L1 arrest (48 hours) of wild-type sleeping worms (N2) and aptf-1(gk794) mutant sleepless worms (HBR227)
2022-02-28 | GSE196158 | GEO
Project description:We report the gene expression in L1 arrest (48 hours) of wild-type sleeping worms (N2) and RIS-manipulated worms (HBR2340 and PHX2193)
2022-02-28 | GSE196380 | GEO
Project description:Cells harbor two systems for the synthesis of fatty acids, one in the cytoplasm (FASN or fatty acid synthase) and one in the mitochondria (mtFAS). In contrast to FASN, mtFAS is poorly characterized, with the major product(s), metabolic roles, and cellular function(s) essentially unknown. Here we show that hypomorphic mtFAS mutants display a profound loss of electron transport chain (ETC) complexes and exhibit compensatory reductive carboxylation. This effect on ETC complexes is independent of the synthesis of lipoic acid, the best characterized function of mtFAS, as mutants lacking lipoic acid synthesis have an intact ETC. Finally, mtFAS impairment blocks the differentiation of skeletal myoblasts in vitro. These data suggest that ETC activity in mammals is profoundly controlled by mtFAS function, thereby connecting anabolic fatty acid synthesis with the oxidation of carbon fuels.
2020-08-17 | GSE148617 | GEO
Project description:Mitochondrial fatty acid synthesis coordinates mitochondrial oxidative metabolism
| PRJNA625208 | ENA
Project description:Adipocytes are the primary sites for fatty acid storage, but the synthesis rate of fatty acids is very low. The physiological significance of this phenomenon remains unclear. Here, we show that surplus fatty acid synthesis in adipocytes induces necroptosis and lipodystrophy. Transcriptional activation of FASN elevates fatty acid synthesis, but decreases NADPH level and increases ROS production, which ultimately leads to adipocyte necroptosis. We identify MED20, a subunit of the Mediator complex, as a negative regulator of FASN transcription. Adipocyte-specific male Med20 knockout mice progressively develop lipodystrophy, which is reversed by scavenging ROS. Further, in a murine model of HIV-associated lipodystrophy and a human patient with acquired lipodystrophy, ROS neutralization significantly improves metabolic disorders, indicating a causal role of ROS in disease onset. Our study well explains the low fatty acid synthesis rate in adipocytes, and sheds light on the management of acquired lipodystrophy.
2023-12-11 | GSE249808 | GEO
Project description:Metabolic remodeling is one of the earliest events that occur during the early differentiation of embryonic stem cells (ESCs), but how these metabolic changes are regulated and participate in the cell differentiation is still largely undissected. Here, we define the fatty acid metabolism as a key player in definitive endoderm (DE) differentiation from human ESCs. During DE differentiation, lipogenesis is decreased while fatty acid β oxidation is enhanced. This dynamic is due to the phosphorylation of lipogenic enzyme acetyl-CoA carboxylase (ACC), which is mediated by AMP-activated protein kinase (AMPK) and inhibits the de novo fatty acid synthesis. More importantly, inhibition of fatty acid synthesis by either its inhibitors or AMPK agonist, significantly promotes the human endoderm differentiation, while blockade of the fatty acid oxidation by genetic manipulation or chemical antagonists impairs the differentiation. The de novo fatty acid synthesis inhibition and fatty acid β oxidation maintaining contribute to the accumulation of cellular acetyl-CoA, which is the essential substrate for protein acetylation. Further study reveals that SMAD3 acetylation and the subsequent subcellular localization exhibit significant change upon interfering fatty acid metabolism. Mechanistically, the accumulation of cellular acetyl-CoA guarantees the acetylation of key transcription factor SMAD3, which further causes the nuclear localization and activation of SMAD signaling pathway to promote DE differentiation. Thus, our current study reveals a fatty acid synthesis/oxidation shift during early differentiation and presents an instructive role of fatty acid metabolism in regulating human early endoderm differentiation.
2023-07-02 | GSE218319 | GEO