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Knockout of the non...
Knockout of the non-essential gene SUGCT creates diet-linked, age-related microbiome disbalance with a diabetes-like metabolic syndrome phenotype
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- Niska-Blakie, Joanna (författare)
- A*Star Institute of Molecular and Cell Biology (IMCB),A*Star, Bioinformatics Institute (BII)
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- Gopinathan, Lakshmi (författare)
- A*Star Institute of Molecular and Cell Biology (IMCB)
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- Low, Kia Ngee (författare)
- A*Star, Bioinformatics Institute (BII)
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- Kien, Yang Lay (författare)
- A*Star, Bioinformatics Institute (BII)
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- Goh, Christine M.F. (författare)
- A*Star Institute of Molecular and Cell Biology (IMCB)
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- Caldez, Matias J. (författare)
- A*Star Institute of Molecular and Cell Biology (IMCB),National University of Singapore
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- Pfeiffenberger, Elisabeth (författare)
- A*Star Institute of Molecular and Cell Biology (IMCB)
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- Jones, Oliver S. (författare)
- A*Star Institute of Molecular and Cell Biology (IMCB)
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- Ong, Chee Bing (författare)
- A*Star Institute of Molecular and Cell Biology (IMCB)
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- Kurochkin, Igor V. (författare)
- A*Star, Bioinformatics Institute (BII)
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- Coppola, Vincenzo (författare)
- Ohio State University
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- Tessarollo, Lino (författare)
- National Cancer Institute at Frederick
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- Choi, Hyungwon (författare)
- A*Star Institute of Molecular and Cell Biology (IMCB),National University of Singapore
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- Kanagasundaram, Yoganathan (författare)
- A*Star, Bioinformatics Institute (BII)
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- Eisenhaber, Frank (författare)
- Nanyang Technological University,A*Star, Bioinformatics Institute (BII)
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- Maurer-Stroh, Sebastian (författare)
- A*Star, Bioinformatics Institute (BII),National University of Singapore
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- Kaldis, Philipp (författare)
- Lund University,Lunds universitet,CRC, Clinical Research Centre,Medicinska fakulteten,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Metabolism och leversjukdomar,CRC, Clinical Research Centre,Faculty of Medicine,Diabetic Complications,Lund University Research Groups,Metabolic disorders and liver disease,A*Star Institute of Molecular and Cell Biology (IMCB),National University of Singapore
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(creator_code:org_t)
- 2019-11-13
- 2019
- Engelska.
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Ingår i: Cellular and Molecular Life Sciences. - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071.
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://link.springe...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- SUGCT (C7orf10) is a mitochondrial enzyme that synthesizes glutaryl-CoA from glutarate in tryptophan and lysine catabolism, but it has not been studied in vivo. Although mutations in Sugct lead to Glutaric Aciduria Type 3 disease in humans, patients remain largely asymptomatic despite high levels of glutarate in the urine. To study the disease mechanism, we generated SugctKO mice and uncovered imbalanced lipid and acylcarnitine metabolism in kidney in addition to changes in the gut microbiome. After SugctKO mice were treated with antibiotics, metabolites were comparable to WT, indicating that the microbiome affects metabolism in SugctKO mice. SUGCT loss of function contributes to gut microbiota dysbiosis, leading to age-dependent pathological changes in kidney, liver, and adipose tissue. This is associated with an obesity-related phenotype that is accompanied by lipid accumulation in kidney and liver, as well as “crown-like” structures in adipocytes. Furthermore, we show that the SugctKO kidney pathology is accelerated and exacerbated by a high-lysine diet. Our study highlights the importance of non-essential genes with no readily detectable early phenotype, but with substantial contributions to the development of age-related pathologies, which result from an interplay between genetic background, microbiome, and diet in the health of mammals.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- C7orf10
- Glutaric aciduria type 3 (GA3)
- Gut microflora
- Lipids
- Metabolomics
- Obesity
- Sugct
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Niska-Blakie, Jo ...
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Gopinathan, Laks ...
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Low, Kia Ngee
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Kien, Yang Lay
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Goh, Christine M ...
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Caldez, Matias J ...
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visa fler...
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Pfeiffenberger, ...
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Jones, Oliver S.
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Ong, Chee Bing
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Kurochkin, Igor ...
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Coppola, Vincenz ...
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Tessarollo, Lino
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Choi, Hyungwon
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Kanagasundaram, ...
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Eisenhaber, Fran ...
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Maurer-Stroh, Se ...
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Kaldis, Philipp
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Cell och molekyl ...
- Artiklar i publikationen
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Cellular and Mol ...
- Av lärosätet
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Lunds universitet