Additional file 12: Figure S1. of Construction of an integrative regulatory element and variation map of the murine Tst locus

Integrated gene transcription regulatory elements for atlas development. Schematic of elements affecting gene transcription and expression at the level of chromatin state (histone modifications, DNA methylation, chromatin accessibility), through transcription factors and RNA polymerase binding, variation impact and microRNAs miRNAs influence. (JPG 1035 kb

Additional file 11: Figure S2. of Construction of an integrative regulatory element and variation map of the murine Tst locus

Primers positions used in sequencing the Tst locus. A) Positions of primers used for amplification of ~ 3 kb segments (A, B, C) of Tst region. B) Location of PCR primers for detailed sequencing of A, B, and C segments. (JPG 4083 kb

Additional file 9: Table S9. of Construction of an integrative regulatory element and variation map of the murine Tst locus

Merged mouse single nucleotide polymorphisms (SNP) from Ensembl and Mouse genomes project (Wellcome Trust Sanger Institute). (DOCX 63 kb

Additional file 8: Table S8. of Construction of an integrative regulatory element and variation map of the murine Tst locus

Predicted miRNA target sites. (DOCX 22 kb

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

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 \u27lean\u27 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. Nat Med 2016 Jul; 22(7):771-9

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

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 \u27lean\u27 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. Nat Med 2016 Jul; 22(7):771-9