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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 (author)
- A*Star, Bioinformatics Institute (BII),A*Star Institute of Molecular and Cell Biology (IMCB)
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- Gopinathan, Lakshmi (author)
- A*Star Institute of Molecular and Cell Biology (IMCB)
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- Low, Kia Ngee (author)
- A*Star, Bioinformatics Institute (BII)
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- Kien, Yang Lay (author)
- A*Star, Bioinformatics Institute (BII)
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- Goh, Christine M.F. (author)
- A*Star Institute of Molecular and Cell Biology (IMCB)
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- Caldez, Matias J. (author)
- A*Star Institute of Molecular and Cell Biology (IMCB),National University of Singapore
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- Pfeiffenberger, Elisabeth (author)
- A*Star Institute of Molecular and Cell Biology (IMCB)
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- Jones, Oliver S. (author)
- A*Star Institute of Molecular and Cell Biology (IMCB)
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- Ong, Chee Bing (author)
- A*Star Institute of Molecular and Cell Biology (IMCB)
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- Kurochkin, Igor V. (author)
- A*Star, Bioinformatics Institute (BII)
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- Coppola, Vincenzo (author)
- Ohio State University
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- Tessarollo, Lino (author)
- National Cancer Institute at Frederick
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- Choi, Hyungwon (author)
- National University of Singapore,A*Star Institute of Molecular and Cell Biology (IMCB)
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- Kanagasundaram, Yoganathan (author)
- A*Star, Bioinformatics Institute (BII)
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- Eisenhaber, Frank (author)
- Nanyang Technological University,A*Star, Bioinformatics Institute (BII)
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- Maurer-Stroh, Sebastian (author)
- National University of Singapore,A*Star, Bioinformatics Institute (BII)
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- Kaldis, Philipp (author)
- 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,National University of Singapore,A*Star Institute of Molecular and Cell Biology (IMCB)
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(creator_code:org_t)
- 2019-11-13
- 2019
- English.
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In: Cellular and Molecular Life Sciences. - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071.
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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
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- C7orf10
- Glutaric aciduria type 3 (GA3)
- Gut microflora
- Lipids
- Metabolomics
- Obesity
- Sugct
Publication and Content Type
- art (subject category)
- ref (subject category)
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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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show more...
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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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- MEDICAL AND HEALTH SCIENCES
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and Basic Medicine
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Cellular and Mol ...
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Lund University