Genetic identification of thiosulfate sulfurtransferase as an adipocyte-expressed antidiabetic target in mice selected for leanness
| Autor: | Sergio Rodriguez-Cuenca, Gary A. Churchill, Antonio Vidal-Puig, Maximilian Zeyda, Nicholas M. Morton, Annalisa Gastaldello, Jasmina Beltram, Scott P. Webster, Gregor Gorjanc, Aila Saari, Thomas M. Stulnig, Simon Horvat, Vilmundur Gudnason, Roderick N. Carter, Matthew T G Gibbins, José Manuel Fernández-Real, Jonathan R. Seckl, Steven C. Munger, Clare McFadden, Gregorio Naredo, Martin E. Barrios-Llerena, Donald R. Dunbar, Christopher J Kenyon, Zhao V. Wang, Alexander F. Howie, Lynne Ramage, José María Moreno-Navarrete, Karen L. Svenson, Brian R. Walker, Valur Emilsson, Petra Sipilä, Zoi Michailidou, Rhona Aird |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adipose tissue Type 2 diabetes Diabetis no-insulinodependent chemistry.chemical_compound Mice Adipocyte Adipocytes Non-insulin-dependent diabetes Gene Knock-In Techniques Molecular Targeted Therapy health care economics and organizations 2. Zero hunger Glucose tolerance test medicine.diagnostic_test Cell Differentiation General Medicine Rhodanese 3. Good health Mitochondria Adipose Tissue Models Animal Obesitat type 2 diabetes obesity-resistance medicine.medical_specialty Transgene education Mice Inbred Strains Mice Transgenic Biology leanness Diet High-Fat Real-Time Polymerase Chain Reaction ta3111 General Biochemistry Genetics and Molecular Biology Article Diabetes Mellitus Experimental 03 medical and health sciences Insulin resistance Internal medicine medicine Animals Humans RNA Messenger Obesity insulin sensitivity genetics Glucose Tolerance Test medicine.disease bacterial infections and mycoses Thiosulfate Sulfurtransferase 030104 developmental biology Endocrinology chemistry Diabetes Mellitus Type 2 quantitative trait loci Glucose Clamp Technique Insulin Resistance Thiosulfate sulfurtransferase |
| Zdroj: | Morton, N M, Beltram, J, Carter, R N, Michailidou, Z, Gorjanc, G, McFadden, C, Barrios-Llerena, M E, Rodriguez-Cuenca, S, Gibbins, M T G, Aird, R E, Moreno-Navarrete, J M, Munger, S C, Svenson, K L, Gastaldello, A, Ramage, L, Naredo, G, Zeyda, M, Wang, Z V, Howie, A F, Saari, A, Sipilä, P, Stulnig, T M, Gudnason, V, Kenyon, C J, Seckl, J R, Walker, B R, Webster, S P, Dunbar, D R, Churchill, G A, Vidal-Puig, A, Fernandez-Real, J M, Emilsson, V & Horvat, S 2016, ' Genetic identification of thiosulfate sulfurtransferase as an adipocyte-expressed antidiabetic target in mice selected for leanness ', Nature Medicine, vol. 22, no. 7, pp. 771-779 . https://doi.org/10.1038/nm.4115 Nature medicine © Nature Medicine, 2016, vol. 22, p. 771-779 Articles publicats (D-CM) DUGiDocs – Universitat de Girona instname |
| Popis: | 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 N. Morton was supported by a Career Development Fellowship, Institutional Strategic Support Fund award and a New Investigator Award from the Wellcome Trust (100981/Z/13/Z), a Research Councils UK Fellowship and a British Heart Foundation Centre of Research Excellence exchange award. We thank the Slovenian Research Agency (core funding P4-0220, project N5-0003 Syntol and J4-6804 to S.H.); and a Young Scientist Fellowship to J. Beltram. We acknowledge support of the British Heart Foundation Research Excellence Award in support of the Bioinformatics Core contribution. T. Stulnig received funding from the Federal Ministry of Economy, Family and Youth and the Austrian National Foundation for Research, Technology and Development. G. Churchill was supported by the US National Institutes of Health grant R01GM 070683. J.M. Fernandez-Real acknowledges funding from FIS PI11/00214. A. Vidal-Puig was funded by the UK Medical Research Council (MRC) MDU, an MRC Programme grant, MRC DMC Core and MITIN (HEALTH-F4-2008-223450) |
| Databáze: | OpenAIRE |
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