Cystathionine gamma-lyase/hydrogen sulfide system is essential for adipogenesis and fat mass accumulation in mice

• Published in: Biochimica et biophysica acta. Molecular and cell biology of lipids 2018-02, Vol.1863 (2), p.165-176
• Main Authors: Yang, Guangdong, Ju, Youngjun, Fu, Ming, Zhang, Yanjie, Pei, Yanxi, Racine, Mélanie, Baath, Simran, Merritt, Thomas J.S., Wang, Rui, Wu, Lingyun
• Format: Article
• Language: English
• Subjects: 3T3-L1 Cells; Adipocytes - metabolism; Adipocytes - pathology; Adipogenesis; Adipose Tissue - metabolism; Adipose Tissue - pathology; Animals; Cell Differentiation - genetics; Cystathionine gamma-lyase; Cystathionine gamma-Lyase - genetics; Cystathionine gamma-Lyase - metabolism; H2S; Hydrogen Sulfide - metabolism; Mice; Mice, Knockout; Obesity; Obesity - genetics; Obesity - metabolism; Obesity - pathology; PPARγ; Response Elements; S-sulfhydration; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 1388-1981; 1879-2618; 1879-2618
• DOI: 10.1016/j.bbalip.2017.11.008

Hydrogen sulfide (H2S) has been recognized as an important gasotransmitter analogous to nitric oxide and carbon monoxide. Cystathionine gamma-lyase (CSE)-derived H2S is implicated in the regulation of insulin resistance and glucose metabolism, but the involvement of CSE/H2S system in energy homeostasis and fat mass has not been extensively explored. In this study, a potential functional role of the CSE/H2S system in in vitro adipocyte differentiation and in vivo adipogenesis and the underlying mechanism was investigated. CSE expression and H2S production were increased during adipocyte differentiation, and that the pattern of CSE mRNA expression was similar to that of CCAAT/enhancer-binding protein (C/EBP) β and δ, two key regulators for adipogenesis. C/EBPβ and γ bind to the CCAAT box in CSE promoter and stimulate CSE gene transcription. H2S induced PPARγ transactivation activity by S-sulfhydrating all the cysteine residues in the DNA binding domain and stimulated adipogenesis. High fat diet-induced fat mass was lost in CSE deficient mice, and exogenously applied H2S promoted fat mass accumulation in fruit flies. In conclusion, CSE/H2S system is essential for adipogenesis and fat mass accumulation through enhancement of PPARγ function in adipocytes. This study suggests that the CSE/H2S system is involved in the pathogenesis of obesity in mice. [Display omitted] •C/EBPβ and δ induce CSE transcription by binding at CCAAT box in CSE promoter.•H2S stimulates PPARγ transactivation by S-sulfhydration.•The CSE/H2S system induces adipocyte differentiation.•Deficiency of CSE prevents high fat diet-induced fat mass in mice.•Direct supplement of H2S donors induce fat mass in fruit flies.