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| Status |
Public on Apr 11, 2016 |
| Title |
Genetic identification of an adipocyte expressed anti-diabetic target in mice selected for resistance to diet-induced obesity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Discovery of genetic mechanisms of resistance to obesity and diabetes may illuminate new therapeutic strategies to tackle this escalating global health burden. We used the polygenic Lean mouse model, selected for low adiposity over 60 generations, to identify thiosulfate sulfur transferase (Tst, rhodanese) as a candidate obesity-resistance gene with selectively increased adipocyte expression. Adipose Tst expression correlated with indices of metabolic health across diverse mouse strains. Transgenic overexpression of Tst in adipocytes protected mice from diet-induced obesity and insulin-resistant diabetes. Tst gene deficiency markedly exacerbated diabetes whereas pharmacological TST activation ameliorated diabetes in mice in vivo. TST selectively augmented mitochondrial function combined with degradation of reactive oxygen species and sulfide. In humans, adipose TST mRNA correlated positively with adipose insulin sensitivity and negatively with fat mass. Genetic identification of Tst as a beneficial regulator of adipocyte mitochondrial function may have therapeutic significance for type 2 diabetes.
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| Overall design |
Illumina 100bp paired-end RNA-seq was profiled from subcutaneous inguinal fat from 24 female 26-week old mice from four inbred strains (C57BL/6J, NZO/HiLtJ, CAST/EiJ, WSB/EiJ) raised on standard chow or high fat diet (3 biological replicates per strain*diet group).
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| Contributor(s) |
Morton NM, Beltram J, Carter RE, Michailidou Z, Gorjanc G, McFadden C, Barrios-Llerena M, Rodiguez-Cuenca S, Gibbins M, Aird RE, Moreno-Navarrete JM, Munger SC, Svenson KL, Gastaldo A, Ramage L, Naredo G, Zeyda M, Wang ZV, Howie AF, Saari A, Sipila P, Stulnig T, Gudnasson V, Kenyon CJ, Seckl JR, Walker BR, Webster SP, Dunbar DR, Churchill GA, Vidal-Puig A, Fernandez-Real JM, Emilsson V, Horvat S |
| Citation missing |
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| Submission date |
Apr 11, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Steven C Munger |
| E-mail(s) |
steven.munger@jax.org
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| Organization name |
The Jackson Laboratory
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| Lab |
Steven Munger
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| Street address |
600 Main Street
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| City |
Bar Harbor |
| State/province |
ME |
| ZIP/Postal code |
04609 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA318057 |
| SRA |
SRP073119 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE80162_Adipose_Genes_Counts_processedmatrix.txt.gz |
1.0 Mb |
(ftp)(http) |
TXT |
| GSE80162_Adipose_Genes_UpperQuartileNormalized_Counts_processedmatrix.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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