The identity of metabolites was confirmed based on the retention time and accurate m/z of authentic synthesized chemical standards from Sigma Aldrich, Cayman Chemical as well as MS2 fragmentation patterns available in HMDB (https://hmdb.ca/) and mzCloud database (https://www.mzcloud.org/).
"],"technology_type":["mass spectrometry assay"],"disease":[""],"extraction_protocol":["For tissue metabolite extraction, frozen and cryo-milled tissue powder (~20 mg) was mixed with 40:40:20 mixture of acetonitrile:methanol:water (extraction solvent) to make 25 mg of tissue/mL of solvent, vortexed, and centrifuged at 16,000 x g for 10 min at 4°C. 3 μL of supernatant was injected into LC-MS. For serum, 150 μL of extraction solvent was added to 5 μL of serum and processed the same as tissue extraction.
"],"organism":["Mus musculus"],"data_transformation_protocol":["Data were analyzed using the EI-MAVEN software and Compound Discoverer software (Thermofisher Scientific).
"],"study_factor":["Diet","Sex","Diet duration"],"metabolights_link":["https://www.ebi.ac.uk/metabolights/MTBLS13977"],"submitter_email":["mirandek@uci.edu"],"sample_collection_protocol":["At 8-9 AM, ad-lib-fed mice were anesthetized with isoflurane using the drop method and placed on a dissection tray with a nose cone. The abdominal cavity was opened with a small incision, and all abdominal organs were moved with fine surgical scissors to reveal the left kidney. The renal vein was identified and then punctured with an insulin syringe. ~20 μL of blood was slowly collected with the syringe, then the renal vein was clamped as the syringe was removed. Renal vein blood was transferred into an Eppendorf tube and stored on ice. Immediately after, the thoracic cavity was quickly opened by cutting through the ribcage and the aorta was cut with fine surgical scissors. ~50 μL of pooled systemic blood in the thoracic cavity was collected with a cut pipet tip, transferred to an Eppendorf tube and stored on ice. Blood collection was completed within 5 minutes post-anesthesia. For serum preparation, blood samples were placed on ice in the anticoagulant-free tube for 20 min, followed by centrifugation at 10,000 x g for 10 minutes at 4ºC. The resulting supernatant was stored at -80ºC and analyzed within one week. The kidney tissues were snap-frozen using a liquid nitrogen-cooled Wollenburg clamp. Tissues were put into 2 mL Eppendorf tubes with a pre-cooled 5 mm metal bead. The cryo-mill (Retsch, Newtown, PA) was pre-cooled before loading 2 mL tubes. Once pre-cooled, the tubes were loaded, and all tissues were milled at 25 Hz for 1-2 minutes. Metal beads were removed, and tissue powder was stored at -80ºC.
"],"repository":["MetaboLights"],"study_status":["Public"],"ptm_modification":[""],"omics_type":["Metabolomics"],"instrument_platform":["Liquid Chromatography MS - positive - hilic","Liquid Chromatography MS - negative - hilic"],"study_design":["Venous Blood","Arterial Blood","targeted metabolite profiling","Ketogenic Diet","Kidney","untargeted metabolite profiling"],"chromatography_protocol":["LC separation was on an Xbridge BEH amide column (2.1 mm x 150 mm, 2.5 µm particle size, 130 pore size; Waters) at 25 °C using a gradient of solvent A (5% acetonitrile in water with 20 mM ammonium acetate and 20 mM ammonium hydroxide) and solvent B (100% acetonitrile). The flow rate was 150 µL/min. The LC gradient was: 0min, 90% B; 2min, 90% B; 3min, 75% B; 7 min, 75% B; 8min, 70% B; 9min, 70% B; 10min, 50% B; 12min, 50% B; 13min, 25% B; 14min, 20% B; 15min, 20% B; 16min, 0% B; 20.5min, 0% B; 21min, 90% B; 25min, 90% B.
"],"publication":["Sex-dependent metabolic remodeling of kidneys revealed by arteriovenous metabolomics. 10.1101/2024.09.02.610869. PMID:39282331"],"curator_keywords":["Venous Blood","Arterial Blood","targeted metabolite profiling","Ketogenic Diet","Kidney","untargeted metabolite profiling"],"submitter_affiliation":["University of California, Irvine"],"submitter_name":["Miranda Emiko Kelly"],"mass_spectrometry_protocol":["Metabolites were analyzed by quadrupole-orbitrap mass spectrometer (Q-Exactive Plus Hybrid Quadrupole-Orbitrap, Thermo Fisher) mass spectrometers coupled to Vanquish UHPLC Systems (Thermo Fisher) via electrospray ionization. MS analysis was acquired in negative and positive ion modes with Full MS scan mode (SIM) from 70 to 830 m/z and 140,000 resolution.
"],"pubmed_abstract":["Sex is a fundamental biological variable important in biomedical research, drug development, clinical trials, and prevention approaches. Among many organs, kidneys are known to exhibit remarkable structural, histological, and pathological differences between sexes. However, whether and how kidneys display distinct metabolic activities between sexes is poorly understood. By developing kidney-specific arteriovenous (AV) metabolomics combined with transcriptomics, we report striking sex differences in both basal metabolic activities and adaptive metabolic remodeling of kidneys after a fat-enriched ketogenic diet (KD), a regimen known to mitigate kidney diseases and improve immunotherapy for renal cancer. At the basal state, female kidneys show highly accumulated aldosterone and various acylcarnitines. In response to the KD, aldosterone levels remain high selectively in females but the sex difference in acylcarnitines disappears. AV data revealed that, under KD, female kidneys avidly take up circulating fatty acids and release 3-hydroxybutyrate (3-HB) whereas male kidneys barely absorb fatty acids but consistently take up 3-HB. Although both male and female kidneys take up gluconeogenic substrates such as glycerol, glutamine and lactate, only female kidneys exhibit net glucose release. Kidney transcriptomics data incompletely predict these sex differences, suggesting post-transcriptional/translational regulation mechanisms. This study provides foundational insights into the sex-dependent and diet-elicited metabolic flexibility of the kidneys in vivo, serving as a unique resource for understanding variable disease prevalence and drug responses between male and female kidneys."],"pubmed_title":["Sex-dependent metabolic remodeling of kidneys revealed by arteriovenous metabolomics."],"pubmed_authors":["Kelly Miranda E ME, Hoffner Lauren A LA, Ramirez Cuauhtemoc B CB, Anica Alexis L AL, Kim Joohwan J, Tong Gregory G, Kim Yeojin Y, Choi Wonsuk W, Jang Kihong K, Alam Yasmine H YH, Jung Sunhee S, Le Johnny J, Tamburini Ian I, Lopez Miranda L ML, Bae Hosung H, Chun Yujin Y, Song Won-Suk WS, Martinez Thomas F TF, Jang Cholsoon C, Lee Gina G"],"additional_accession":[]},"is_claimable":false,"name":"Sex-dependent metabolic remodeling of kidneys revealed by arteriovenous metabolomics","description":"Sex is a fundamental biological variable important in biomedical research, drug development, clinical trials, and prevention approaches. Among many organs, kidneys are known to exhibit remarkable structural, histological, and pathological differences between sexes. However, whether and how kidneys display distinct metabolic activities between sexes is poorly understood. By developing kidney-specific arteriovenous (AV) metabolomics combined with transcriptomics, we report striking sex differences in both basal metabolic activities and adaptive metabolic remodeling of kidneys after a fat-enriched ketogenic diet (KD), a regimen known to mitigate kidney diseases and improve immunotherapy for renal cancer. At the basal state, female kidneys show highly accumulated aldosterone and various acylcarnitines. In response to the KD, aldosterone levels remain high selectively in females but the sex difference in acylcarnitines disappears. AV data revealed that, under KD, female kidneys avidly take up circulating fatty acids and release 3-hydroxybutyrate (3-HB) whereas male kidneys barely absorb fatty acids but consistently take up 3-HB. Although both male and female kidneys take up gluconeogenic substrates such as glycerol, glutamine and lactate, only female kidneys exhibit net glucose release. Kidney transcriptomics data incompletely predict these sex differences, suggesting post-transcriptional/translational regulation mechanisms. This study provides foundational insights into the sex-dependent and diet-elicited metabolic flexibility of the kidneys in vivo, serving as a unique resource for understanding variable disease prevalence and drug responses between male and female kidneys.
","dates":{"publication":"2026-03-04","submission":"2026-03-04"},"accession":"MTBLS13977","cross_references":{"pubmed":["39282331"]}}