Genetic identification of thiosulfate sulfurtransferase as an adipocyte-expressed antidiabetic target in mice selected for leanness.

Autor: Morton NM; University-British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK., Beltram J; Biotechnical Faculty, Animal Science Department, University of Ljubljana, Ljubljana, Slovenia., Carter RN; University-British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK., Michailidou Z; University-British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK., Gorjanc G; Biotechnical Faculty, Animal Science Department, University of Ljubljana, Ljubljana, Slovenia., McFadden C; University-British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK., Barrios-Llerena ME; University-British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK., Rodriguez-Cuenca S; Metabolic Research Laboratories, Level 4, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrookes Hospital, Cambridge, UK., Gibbins MT; University-British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK., Aird RE; University-British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK., Moreno-Navarrete JM; Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomédica de Girona, Girona, Spain.; Department of Medicine, University of Girona, Girona, Spain.; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Girona, Spain., Munger SC; The Jackson Laboratory, Bar Harbor, Maine, USA., Svenson KL; The Jackson Laboratory, Bar Harbor, Maine, USA., Gastaldello A; University-British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK., Ramage L; University-British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK., Naredo G; University-British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK., Zeyda M; Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria., Wang ZV; Department of Internal Medicine, Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA., Howie AF; The Medical Research Council (MRC) Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK., Saari A; Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland., Sipilä P; Central Animal Laboratory, University of Turku, Turku, Finland., Stulnig TM; Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria., Gudnason V; Icelandic Heart Association, Kopavogur, Iceland., Kenyon CJ; University-British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK., Seckl JR; University-British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK., Walker BR; University-British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK., Webster SP; University-British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK., Dunbar DR; University-British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK., Churchill GA; The Jackson Laboratory, Bar Harbor, Maine, USA., Vidal-Puig A; Metabolic Research Laboratories, Level 4, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrookes Hospital, Cambridge, UK.; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK., Fernandez-Real JM; Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomédica de Girona, Girona, Spain.; Department of Medicine, University of Girona, Girona, Spain.; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Girona, Spain., Emilsson V; Icelandic Heart Association, Kopavogur, Iceland.; Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland., Horvat S; Biotechnical Faculty, Animal Science Department, University of Ljubljana, Ljubljana, Slovenia.; National Institute of Chemistry, Ljubljana, Slovenia.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2016 Jul; Vol. 22 (7), pp. 771-9. Date of Electronic Publication: 2016 Jun 06.
DOI: 10.1038/nm.4115
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz: