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| Status |
Public on Feb 05, 2024 |
| Title |
Transcriptomic signature of white adipose tissue from wild type and Acod1-deficient mice in response to high fat diet |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Aconitate decarboxylase 1 (ACOD1) is the enzyme synthesizing itaconate, an immuno-regulatory metabolite tuning host-pathogen interactions. Such functions are achieved by affecting metabolic pathways regulating inflammation and microbe survival. However, at the whole-body level, metabolic roles of itaconate remain largely unresolved. By using multiomics-integrated approaches, here we show that ACOD1 responds to high-fat diet consumption in mice by promoting gut microbiota alterations supporting metabolic disease. Genetic disruption of itaconate biosynthesis protects mice against obesity, alterations in glucose homeostasis and liver metabolic dysfunctions by decreasing meta-inflammatory responses to dietary lipid overload. Mechanistically, fecal metagenomics and microbiota transplantation experiments demonstrate such effects are dependent on an amelioration of the intestinal ecosystem composition, skewed by high-fat diet feeding towards obesogenic phenotype. In particular, unbiased fecal microbiota profiling and axenic culture experiments point towards a primary role for itaconate in inhibiting growth of Bacteroidaceae and Bacteroides, family and genus of Bacteroidetes phylum, the major gut microbial taxon associated with metabolic health. Specularly to the effects imposed by Acod1 deficiency on fecal microbiota, oral itaconate consumption enhances diet-induced gut dysbiosis and associated obesogenic responses in mice. Unveiling an unrecognized role of itaconate, either endogenously produced or exogenously administered, in supporting microbiota alterations underlying diet-induced obesity in mice, our study points ACOD1 as a target against inflammatory consequences of overnutrition.
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| Overall design |
Gene expression profiling was performed using data obtained from RNA-seq derived from inguinal (iWAT) and epididymal (eWAT) white adipose tissues from wild type mice receiving normal chow diet and high fat diet (HFD) (60% kalories from fat) and Acod1-/- mice receiving HFD.
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| Contributor(s) |
Simone C, Tanja E |
| Citation(s) |
38302438 |
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| Submission date |
Sep 19, 2022 |
| Last update date |
Feb 05, 2024 |
| Contact name |
Tanja Eberhart |
| Organization name |
IRCCS San Raffaele Scientific Institute
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| Street address |
Via Olgettina
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| City |
Milan |
| ZIP/Postal code |
20132 |
| Country |
Italy |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (25)
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| Relations |
| BioProject |
PRJNA882000 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE213632_RAW.tar |
11.1 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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