Specific downregulation of cystathionine β-synthase expression in the kidney during obesity

Hydrogen sulfide (H₂ S) is recognized as a novel gasotransmitter involved in the regulation of nervous system, cardiovascular functions, inflammatory response, gastrointestinal system, and renal function. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are the major enzymes responsible for H₂ S production through desulfuration reactions. H₂ S is reported to play a protective role in both high-fat diet (HFD)-induced obese and diabetic mice. However, the synthesizing enzyme involved is not clearly elucidated. The current study was aimed to investigate the regulation of CBS and CSE in different tissues including the kidney, liver, and epididymal fat in C57BL/6 mice after a HFD (60% kcal fat) for 24 weeks. The protein and mRNA expression of CBS was specifically decreased in the kidney while CSE remained unchanged, which was further confirmed in db/db mice. In the liver, CSE expression was downregulated after HFD accompanied with unchanged CBS. Moreover, CSE expression was even upregulated in epididymal fat. The specific downregulation of renal CBS may contribute to decreased H₂ S production, which could be a pathogenic mechanism of obesity. Increased CSE/H₂ S pathway in epididymal fat possibly resulted in impaired glucose uptake and aggravated insulin resistance. In conclusion, our results revealed that CBS was selectively downregulated in both diet and gene-induced obesity models.