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Clinical research

Morbidly obese subjects show increased serum sulfide in proportion to fat mass

International Journal of Obesity volume 45, pages 415–426 (2021)Cite this article

Subjects

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.

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Fig. 1: Serum sulfide in association with obesity, fat mass and fasting glucose in cohort 1.
Fig. 2: Serum sulfide in association with obesity and fat mass in cohort 2.

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Acknowledgements

This work was partially supported by research grants PI15/01934, PI16/01173 and PI19/01712 from the Instituto de Salud Carlos III from Spain and VII Spanish Diabetes Association grants to Basic Diabetes Research Projects led by young researchers, CIBEROBN Fisiopatología de la Obesidad y Nutrición is an initiative from the Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER) from Spain. Project ThinkGut (EFA345/19) 65% co-financed by the European Regional Development Fund (ERDF) through the Interreg V-A Spain-France-Andorra programme (POCTEFA 2014-2020). We acknowledge the technical assistance of Oscar Rovira (IdIBGi). We want to particularly acknowledge the patients, the FATBANK platform promoted by the CIBEROBN and the IDIBGI Biobank (Biobanc IDIBGI, B.0000872), integrated in the Spanish National Biobanks’ Network, for their collaboration and coordination.

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Authors and Affiliations

  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

    Ferran Comas, Jèssica Latorre, Francisco Ortega, María Arnoriaga Rodríguez, Aina Lluch, Mònica Sabater, Wifredo Ricart, José Manuel Fernández-Real & José María Moreno-Navarrete

  2. Endocrinology and Nutrition Department, University Hospital Arnau de Vilanova, Obesity, Diabetes and Metabolism (ODIM) research group, IRBLleida, University of Lleida, Lleida, Spain

    Ferran Rius & Albert Lecube

  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

    Xavier Ribas & Miquel Costas

  4. Department of Medicine, Universitat de Girona, Girona, Spain

    Wifredo Ricart, José Manuel Fernández-Real & José María Moreno-Navarrete

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  1. Ferran Comas
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Correspondence to José Manuel Fernández-Real or José María Moreno-Navarrete.

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Comas, F., Latorre, J., Ortega, F. et al. Morbidly obese subjects show increased serum sulfide in proportion to fat mass. Int J Obes 45, 415–426 (2021). https://doi.org/10.1038/s41366-020-00696-z

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