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, selected for low adiposity over 60 generations, to identify thiosulfate sulfurtransferase (Tst, Rhodanese) as a candidate obesity-resistance gene with selectively increased adipocyte expression. 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 gene deficiency markedly exacerbated diabetes whereas pharmacological TST activation ameliorated diabetes in mice in vivo. Mechanistically, 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.

BackgroundHigh-sensitivity cardiac troponin assays may improve the diagnosis of myocardial infarction but increase the detection of elevated cardiac troponin in patients without acute coronary syndrome.MethodsIn a prospective cohort study, we evaluated the prevalence, determinants, and outcome of patients with elevated cardiac troponin attending the emergency department without suspected acute coronary syndrome. We measured high-sensitivity cardiac troponin in 918 consecutive patients attending the emergency department without suspected acute coronary syndrome who had blood sampling performed by the attending clinician. Elevated high-sensitivity cardiac troponin I was defined as concentrations above the sex-specific 99th percentile threshold. Clinical demographics, physiological measures, and all-cause mortality at 1 year associated with elevated high-sensitivity cardiac troponin concentrations were recorded.ResultsElevated cardiac troponin concentration occurred in 114 (12.4%) patients, of whom 2 (0.2%), 3 (0.3%), and 109 (11.9%) were adjudicated as type 1 myocardial infarction, type 2 myocardial infarction, and myocardial injury, respectively. Elevated troponin concentrations were associated with increasing age, worsening renal function, multimorbidity, and adverse physiology. Across a total of 912 patient-years follow-up, cardiac troponin concentration was a strong predictor of death (hazard ratio [HR] 1.26 per 2-fold increase, 95% confidence interval [CI] 1.06 to 1.49) independent of age, sex, multimorbidity, and adverse physiology.ConclusionsHigh-sensitivity cardiac troponin concentrations were elevated in 1 in 8 consecutive patients without suspected acute coronary syndrome attending the emergency department and were associated with increasing age, multimorbidity, adverse physiology, and death. Elevated cardiac troponin in unselected patients predominantly reflects myocardial injury rather than myocardial infarction.

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