ArticleCellular and molecular life sciences : CMLS2020
Knockout of the non-essential gene SUGCT creates diet-linked, age-related microbiome disbalance with a diabetes-like metabolic syndrome phenotype.
Article in Cellular and molecular life sciences : CMLS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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18 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
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- Enteric bacterial infection stimulates remodelling of bile metabolites to promote intestinal homeostasis.Nature microbiology · 2024Article
- Whole exome sequencing reveals a dual diagnosis ofMolecular genetics and metabolism reports · 2024Article
- A novel support vector machine-based 1-day, single-dose prediction model of genotoxic hepatocarcinogenicity in rats.Archives of toxicology · 2024Article
- Characterization, Structure, and Inhibition of the Human Succinyl-CoA:glutarate-CoA Transferase, a Putative Genetic Modifier of Glutaric Aciduria Type 1.ACS chemical biology · 2024Article
- Genomic insights into local adaptation and phenotypic diversity of Wenchang chickens.Poultry science · 2024Article
- Characterization, structure and inhibition of the human succinyl-CoA:glutarate-CoA transferase, a genetic modifier of glutaric aciduria type 1.bioRxiv : the preprint server for biology · 2024Article
- Major urinary protein (Microbiology spectrum · 2024Article
- Spatial Pathomics Toolkit for Quantitative Analysis of Podocyte Nuclei with Histology and Spatial Transcriptomics Data in Renal Pathology.Proceedings of SPIE--the International Society for Optical Engineering · 2024Article
- Point-of-care applicable metabotyping using biofluid-specific electrospun MetaSAMPs directly amenable to ambient LA-REIMS.Science advances · 2023Article
- Case report: Paternal uniparental disomy on chromosome 7 and homozygousFrontiers in genetics · 2023Article
- LINE-1 promotes tumorigenicity and exacerbates tumor progression via stimulating metabolism reprogramming in non-small cell lung cancer.Molecular cancer · 2022Article
- Genome-wide scan for selection signatures and genes related to heat tolerance in domestic chickens in the tropical and temperate regions in Asia.Poultry science · 2022Article
- 3D disorganization and rearrangement of genome provide insights into pathogenesis of NAFLD by integrated Hi-C, Nanopore, and RNA sequencing.Acta pharmaceutica Sinica. B · 2021Article
- Host genetic control of gut microbiome composition.Mammalian genome : official journal of the International Mammalian Genome Society · 2021Review
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17 authors at 4 institutions in 3 countries.
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Abstract
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.
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