Summary of Study ST004252
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002681. The data can be accessed directly via it's Project DOI: 10.21228/M83R9T This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST004252 |
| Study Title | Acetyl-CoA Carboxylase Maintains Energetic Balance for Functional Oogenesis |
| Study Summary | Summary of the study Reproduction is closely tied to nutrient intake and lipid metabolism, with imbalances often leads to reproductive failure. We characterized the metabolic mechanisms mediated by Acetyl-CoA Carboxylase (ACC, a rate-limiting enzyme for fatty acid synthesis) that support oogenesis and discovered that ACC regulates nutrient-responsive TOR signaling to maintain endosomal trafficking, crucial for oocyte determination. ACC deficiency shifts metabolism toward fatty acid oxidation (FAO), fueling the TCA cycle and electron transport chain (ETC), which hyperactivates TOR signaling. This results in excessive protein synthesis, disrupting endosomal trafficking and impairing germ cell differentiation. Restoring balance through FAO or TOR inhibition, reducing protein synthesis, or adjusting dietary protein intake corrects these defects. Our findings reveal a critical link between lipid metabolism and nutrient-sensing pathways in oogenesis, offering potential therapeutic strategies for metabolic disorders affecting reproduction. |
| Institute | Academia Sinica |
| Department | ICOB |
| Laboratory | Hsu Lab |
| Last Name | Amartuvshin |
| First Name | Oyundari |
| Address | No. 128, Section 2, Academia Rd, Nangang District, Taipei City, Taiwan 115 |
| oyundariamar@gmail.com | |
| Phone | 886-227871542 |
| Submit Date | 2025-09-20 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | GC-MS |
| Release Date | 2025-10-16 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002681 |
| Project DOI: | doi: 10.21228/M83R9T |
| Project Title: | Acetyl-CoA Carboxylase Maintains Energetic Balance for Functional Oogenesis |
| Project Type: | MS quantitative analysis |
| Project Summary: | PROJECT SUMMARY Reproduction requires the integration of nutrient availability and lipid metabolism to sustain oogenesis and ensure fertility. Disruptions in this metabolic balance are strongly associated with reproductive failure, yet the mechanisms that coordinate these processes remain poorly defined. This project aimed to dissect how lipid metabolic pathways intersect with nutrient-sensing signals to govern germ cell differentiation. Specifically, we focused on the role of Acetyl-CoA Carboxylase (ACC), the rate-limiting enzyme for fatty acid synthesis, in maintaining oocyte development. We demonstrate that ACC functions as a key metabolic regulator by sustaining endosomal trafficking and modulating nutrient-responsive TOR signalling. Loss of ACC activity shifts metabolism toward fatty acid oxidation (FAO), which increases flux through the tricarboxylic acid (TCA) cycle and electron transport chain (ETC). This altered metabolic state hyperactivates TOR signalling, leading to excessive protein synthesis, disrupted endosomal trafficking, and impaired germ cell fate determination. Importantly, we show that these defects are reversible. Targeted interventions—including inhibition of FAO or TOR signalling, attenuation of protein synthesis, or dietary protein adjustment—restore cellular homeostasis and rescue oogenic defects. The findings from this study reveal a previously unrecognised link between lipid metabolism, nutrient-sensing pathways, and reproductive development. By defining ACC as a central coordinator of metabolic and signalling networks in oogenesis, this work advances fundamental understanding of how energy metabolism shapes reproductive outcomes. Furthermore, the identification of corrective strategies highlights potential therapeutic avenues for addressing infertility and reproductive disorders associated with metabolic imbalance. |
| Institute: | Academia Sinica |
| Department: | Institute of Cellular and Organismic Biology |
| Laboratory: | R337, Hsu Lab |
| Last Name: | Amamrtuvshin |
| First Name: | Oyundari |
| Address: | R337, ICOB, No. 128, Section 2, Academia Rd, Nangang District, Taipei City, Taiwan 115 |
| Email: | oyundariamar@gmail.com |
| Phone: | 886-227871542 |
Subject:
| Subject ID: | SU004404 |
| Subject Type: | Invertebrate |
| Subject Species: | Drosophila melanogaster |
| Taxonomy ID: | 7227 |
| Genotype Strain: | nos>mCherryRNAi and nos>ACCRNAi |
Factors:
Subject type: Invertebrate; Subject species: Drosophila melanogaster (Factor headings shown in green)
| mb_sample_id | local_sample_id | Sample source | Treatment |
|---|---|---|---|
| SA496506 | AccKD1-2 | Drosophila ovary | Acc knockdown |
| SA496507 | AccKD5-2 | Drosophila ovary | Acc knockdown |
| SA496508 | AccKD5-1 | Drosophila ovary | Acc knockdown |
| SA496509 | AccKD4-2 | Drosophila ovary | Acc knockdown |
| SA496510 | AccKD4-1 | Drosophila ovary | Acc knockdown |
| SA496511 | AccKD3-2 | Drosophila ovary | Acc knockdown |
| SA496512 | AccKD3-1 | Drosophila ovary | Acc knockdown |
| SA496513 | AccKD2-2 | Drosophila ovary | Acc knockdown |
| SA496514 | AccKD2-1 | Drosophila ovary | Acc knockdown |
| SA496515 | AccKD1-1 | Drosophila ovary | Acc knockdown |
| SA496516 | mcherryKD1-2 | Drosophila ovary | control |
| SA496517 | mcherryKD5-2 | Drosophila ovary | control |
| SA496518 | mcherryKD5-1 | Drosophila ovary | control |
| SA496519 | mcherryKD4-2 | Drosophila ovary | control |
| SA496520 | mcherryKD4-1 | Drosophila ovary | control |
| SA496521 | mcherryKD3-2 | Drosophila ovary | control |
| SA496522 | mcherryKD3-1 | Drosophila ovary | control |
| SA496523 | mcherryKD2-2 | Drosophila ovary | control |
| SA496524 | mcherryKD2-1 | Drosophila ovary | control |
| SA496525 | mcherryKD1-1 | Drosophila ovary | control |
| Showing results 1 to 20 of 20 |
Collection:
| Collection ID: | CO004397 |
| Collection Summary: | Collection summary Extraction solution (2:2:1 acetonitrile: methanol: ddH2O) was prepared and stored overnight at -20 degree before usage. Fifty pairs of ovaries from each genotype were dissected in cold 1xPBS. Since nos>ACC RNAi ovaries lacked vitellogenic egg chambers, the vitellogenic egg chambers from control ovaries were removed using forceps, leaving the transparent regions for metabolite extraction. Drosophila dissection was completed within 1 hour. Ovary samples for each genotype were collected in an Eppendorf and metabolites from each sample (containing about 12.5 µg DNA) were extracted using 200 µl metabolite extraction solvent. Samples were homogenized by vortexing for 5 sec followed by cold bath sonication for 5 min, repeated twice. Tissue debris was pelleted by centrifugation at 15871x g (rcf) for 10 min at 4°C. A total of 200 µl metabolite- containing supernatant was transferred into a new tube. The supernatant was freeze-dried for at least 3 h using a freeze drier (VirTis BenchTop K). Dried samples were kept at -80°C until analysed for amino acids and TCA cycle byproducts. |
| Collection Protocol Filename: | TCAcycle_AminoAcid_protocol.docx |
| Sample Type: | Ovaries |
| Collection Method: | Drosophila ovary dissection in 1xPBS |
| Collection Location: | Taiwan |
| Collection Duration: | within 1 hour |
| Storage Conditions: | -80℃ |
| Collection Vials: | Eppendorf |
| Storage Vials: | Eppendorf |
Treatment:
| Treatment ID: | TR004413 |
| Treatment Summary: | noGAL4 virgins were crossed with either mCherryRNAi or AccRNAi flies. Eggs were laid and allowed to develop into adults at 18 °C. Adult flies were then shifted to 29 °C to increase the expression of RNAi in the germline for 7 days. The food was changed daily. |
Sample Preparation:
| Sampleprep ID: | SP004410 |
| Sampleprep Summary: | Fifty pairs of ovaries from each genotype were dissected in cold 1xPBS. Since nos>ACC RNAi ovaries lacked vitellogenic egg chambers, the vitellogenic egg chambers from control ovaries were removed using forceps, leaving the transparent regions for metabolite extraction. Metabolites from each sample (containing about 12.5 µg DNA) were extracted using 200 µL metabolite extraction solvent (2:2:1 acetonitrile: methanol: ddH2O) and stored at -20°C overnight. Samples were homogenized by vortexing for 5 sec followed by cold bath sonication for 5 min, repeated twice. Tissue debris was pelleted by centrifugation at 15871x g (rcf) for 10 min at 4°C. A total of 200 µL metabolite- containing supernatant was transferred into a new tube. The supernatant was freeze-dried for at least 3 h using a freeze drier (VirTis BenchTop K). Dried samples were kept at -80°C until analyzed for amino acids and TCA cycle byproducts. |
Chromatography:
| Chromatography ID: | CH005372 |
| Chromatography Summary: | The samples were derivatized by bis(trimethylsilyl)- trifluoroacetamide (BSTFA) containing 1% trimethylchlorosilane (TMCS) and analyzed using Agilent 7890B gas chromatography coupled with 7250 quadrupole time-of-flight mass spectrometer (GC-Q-TOF/MS) equipped with electron ionization (EI). The separation was performed on Zorbax DB5- MS+10 m Duragard Capillary Column (30 m x 0.25 mm x 0.25 mm, Agilent). The GC temperature profile was held at 60℃ for 1 minutes and then raised at 10℃/min to 325℃ and held at 325℃ for 10 minutes. The transfer line and the ion source temperature were set at 300 ºC and 280 ºC, respectively. The mass-range monitored was from 50 to 600 Daltons. The data acquisition and analysis were performed on MassHunter Workstation software. Mass spectra were compared against the NIST 2017, Fiehn and Wiley Registry 11th Edition mass spectral library. The Agilent MassHunter Unknows Analysis software was used for deconvolution of the signals. The results were imported into the Agilent Mass Profiler Professional software (Agilent Technologies,15.1, Santa Clara, CA, USA) for further peak alignment. |
| Instrument Name: | Agilent 7890B |
| Column Name: | Zorbax DB5- MS+10 m Duragard Capillary Column (30 m x 0.25 mm x 0.25 mm) |
| Column Temperature: | 300ºC |
| Flow Gradient: | 60℃ for 1 minutes and then raised at 10℃/min to 325℃ and held at 325℃ for 10 minutes |
| Flow Rate: | 1 mL/min |
| Solvent A: | Not Applicable |
| Solvent B: | Not Applicable |
| Chromatography Type: | GC |
Analysis:
| Analysis ID: | AN007075 |
| Analysis Type: | MS |
| Chromatography ID: | CH005372 |
| Num Factors: | 2 |
| Num Metabolites: | 6 |
| Units: | peak area |
