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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Bibtex

@article{005a2a538b9b488c9822a2f219dfae6a,
title = "Knockout of the non-essential gene SUGCT creates diet-linked, age-related microbiome disbalance with a diabetes-like metabolic syndrome phenotype",
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.",
keywords = "C7orf10, Glutaric aciduria type 3 (GA3), Gut microflora, Lipids, Metabolomics, Obesity, Sugct",
author = "Joanna Niska-Blakie and Lakshmi Gopinathan and Low, {Kia Ngee} and Kien, {Yang Lay} and Goh, {Christine M.F.} and Caldez, {Matias J.} and Elisabeth Pfeiffenberger and Jones, {Oliver S.} and Ong, {Chee Bing} and Kurochkin, {Igor V.} and Vincenzo Coppola and Lino Tessarollo and Hyungwon Choi and Yoganathan Kanagasundaram and Frank Eisenhaber and Sebastian Maurer-Stroh and Philipp Kaldis",
year = "2019",
month = "11",
doi = "10.1007/s00018-019-03359-z",
language = "English",
journal = "Cellular and Molecular Life Sciences",
issn = "1420-9071",
publisher = "Birkh{\"a}user Verlag",

}