Ferran Comas1, Jèssica Latorre1, Francisco Ortega1, María Arnoriaga Rodríguez1, Aina Lluch1, Mònica Sabater1, Ferran Rius2, Xavier Ribas3, Miquel Costas3, Wifredo Ricart1,4, Albert Lecube2, José Manuel Fernández-Real5,6, José María Moreno-Navarrete7,8. 1. Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, Spain. 2. Endocrinology and Nutrition Department, University Hospital Arnau de Vilanova, Obesity, Diabetes and Metabolism (ODIM) research group, IRBLleida, University of Lleida, Lleida, Spain. 3. Grup de Química Bioinspirada, Supramolecular i Catàlisi (QBIS-CAT), Institut de Química Computacional i Catàlisi (IQCC), Departament de Química, Universitat de Girona, C/M. Aurèlia Capmany 69, 17003, Girona, Spain. 4. Department of Medicine, Universitat de Girona, Girona, Spain. 5. Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, Spain. jmfreal@idibgi.org. 6. Department of Medicine, Universitat de Girona, Girona, Spain. jmfreal@idibgi.org. 7. Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, Spain. jmoreno@idibgi.org. 8. Department of Medicine, Universitat de Girona, Girona, Spain. jmoreno@idibgi.org.
Abstract
BACKGROUND AND OBJECTIVES: The importance of hydrogen sulfide is increasingly recognized in the pathophysiology of obesity and type 2 diabetes in animal models. Very few studies have evaluated circulating sulfides in humans, with discrepant results. Here, we aimed to investigate serum sulfide levels according to obesity. SUBJECTS AND METHODS: Serum sulfide levels were analyzed, using a selective fluorescent probe, in two independent cohorts [cross-sectionally in discovery (n = 139) and validation (n = 71) cohorts, and longitudinally in 82 participants from discovery cohort]. In the validation cohort, blood gene expression of enzymes contributing to H2S generation and consumption were also measured. RESULTS: In the discovery cohort, serum sulfide concentration was significantly increased in subjects with morbid obesity at baseline and follow-up, and positively correlated with BMI and fat mass, but negatively with total cholesterol, haemoglobin, serum ferritin, iron and bilirubin after adjusting by age, gender and fat mass. Fat mass (β = 0.51, t = 3.67, p < 0.0001) contributed independently to age-, gender-, insulin sensitivity- and BMI-adjusted serum sulfide concentration variance. Importantly, receiver operating characteristic analysis demonstrated the relevance of fat mass predicting serum sulfide levels, which was replicated in the validation cohort. In addition, serum sulfide concentration was decreased in morbidly obese subjects with impaired compared to those with normal fasting glucose. Longitudinally, weight gain resulted in increased serum sulfide concentration, whereas weight loss had opposite effects, being the percent change in serum sulfide positively correlated with the percent change in BMI and waist circumference, but negatively with bilirubin. Whole blood CBS, CTH, MPST, SQOR, TST and MPO gene expression was not associated to obesity or serum sulfide concentration. CONCLUSIONS: Altogether these data indicated that serum sulfide concentrations were increased in subjects with morbid obesity in proportion to fat mass and inversely associated with circulating markers of haem degradation.
BACKGROUND AND OBJECTIVES: The importance of hydrogen sulfide is increasingly recognized in the pathophysiology of obesity and type 2 diabetes in animal models. Very few studies have evaluated circulating sulfides in humans, with discrepant results. Here, we aimed to investigate serum sulfide levels according to obesity. SUBJECTS AND METHODS: Serum sulfide levels were analyzed, using a selective fluorescent probe, in two independent cohorts [cross-sectionally in discovery (n = 139) and validation (n = 71) cohorts, and longitudinally in 82 participants from discovery cohort]. In the validation cohort, blood gene expression of enzymes contributing to H2S generation and consumption were also measured. RESULTS: In the discovery cohort, serum sulfide concentration was significantly increased in subjects with morbid obesity at baseline and follow-up, and positively correlated with BMI and fat mass, but negatively with total cholesterol, haemoglobin, serum ferritin, iron and bilirubin after adjusting by age, gender and fat mass. Fat mass (β = 0.51, t = 3.67, p < 0.0001) contributed independently to age-, gender-, insulin sensitivity- and BMI-adjusted serum sulfide concentration variance. Importantly, receiver operating characteristic analysis demonstrated the relevance of fat mass predicting serum sulfide levels, which was replicated in the validation cohort. In addition, serum sulfide concentration was decreased in morbidly obese subjects with impaired compared to those with normal fasting glucose. Longitudinally, weight gain resulted in increased serum sulfide concentration, whereas weight loss had opposite effects, being the percent change in serum sulfide positively correlated with the percent change in BMI and waist circumference, but negatively with bilirubin. Whole blood CBS, CTH, MPST, SQOR, TST and MPO gene expression was not associated to obesity or serum sulfide concentration. CONCLUSIONS: Altogether these data indicated that serum sulfide concentrations were increased in subjects with morbid obesity in proportion to fat mass and inversely associated with circulating markers of haem degradation.
Authors: M Whiteman; K M Gooding; J L Whatmore; C I Ball; D Mawson; K Skinner; J E Tooke; A C Shore Journal: Diabetologia Date: 2010-04-23 Impact factor: 10.122
Authors: Zoltán Pálinkás; Paul G Furtmüller; Attila Nagy; Christa Jakopitsch; Katharina F Pirker; Marcin Magierowski; Katarzyna Jasnos; John L Wallace; Christian Obinger; Péter Nagy Journal: Br J Pharmacol Date: 2014-09-05 Impact factor: 8.739
Authors: Nicholas M Morton; Jasmina Beltram; Roderick N Carter; Zoi Michailidou; Gregor Gorjanc; Clare McFadden; Martin E Barrios-Llerena; Sergio Rodriguez-Cuenca; Matthew T G Gibbins; Rhona E Aird; José Maria Moreno-Navarrete; Steven C Munger; Karen L Svenson; Annalisa Gastaldello; Lynne Ramage; Gregorio Naredo; Maximilian Zeyda; Zhao V Wang; Alexander F Howie; Aila Saari; Petra Sipilä; Thomas M Stulnig; Vilmundur Gudnason; Christopher J Kenyon; Jonathan R Seckl; Brian R Walker; Scott P Webster; Donald R Dunbar; Gary A Churchill; Antonio Vidal-Puig; José Manuel Fernandez-Real; Valur Emilsson; Simon Horvat Journal: Nat Med Date: 2016-06-06 Impact factor: 53.440