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Abstract
The discovery of genetic mechanisms for resistance to obesity and diabetes may illuminate new therapeutic strategies for the treatment of this global health challenge. We used the polygenic 'lean' mouse model, which has been selected for low adiposity over 60 generations, to identify mitochondrial thiosulfate sulfurtransferase (Tst; also known as rhodanese) as a candidate obesity-resistance gene with selectively increased expression in adipocytes. Elevated 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-deficient mice showed markedly exacerbated diabetes, whereas pharmacological activation of TST ameliorated diabetes in mice. Mechanistically, TST selectively augmented mitochondrial function combined with degradation of reactive oxygen species and sulfide. In humans, TST mRNA expression in adipose tissue correlated positively with insulin sensitivity in adipose tissue and negatively with fat mass. Thus, the genetic identification of Tst as a beneficial regulator of adipocyte mitochondrial function may have therapeutic significance for individuals with type 2 diabetes.
Original language | English |
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Pages (from-to) | 771-779 |
Number of pages | 9 |
Journal | Nature Medicine |
Volume | 22 |
Issue number | 7 |
Early online date | 6 Jun 2016 |
DOIs | |
Publication status | Published - Jul 2016 |
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Dive into the research topics of 'Genetic identification of thiosulfate sulfurtransferase as an adipocyte-expressed antidiabetic target in mice selected for leanness'. Together they form a unique fingerprint.Projects
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Profiles
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Gregor Gorjanc
- Royal (Dick) School of Veterinary Studies - Group Leader
- Global Academy of Agriculture and Food Systems
Person: Academic: Research Active
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Nicholas Morton
- Deanery of Clinical Sciences - Personal Chair of Molecular Metabolism
- Centre for Cardiovascular Science
Person: Academic: Research Active