High fat diet stimulates hepatic cystathionine β-synthase and cystathionine γ-lyase expression.

Hwang, S.Y., Sarna, L.K., Siow, Y.L., and O, K. (2013). "High fat diet stimulates hepatic cystathionine β-synthase and cystathionine γ-lyase expression.", Canadian Journal of Physiology and Pharmacology. doi : 10.1139/cjpp-2013-0106  Access to full text


Cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) catalyze homocysteine (Hcy) metabolism via the transsulfuration pathway. They are also responsible for hydrogen sulfide (H2S) production via desulfuration reactions. The liver contributes significantly to the regulation of Hcy and H2S homeostasis which might participate in many physiological and pathological processes. The aim of this study was to investigate the effect of a high fat diet (HFD) on hepatic CBS and CSE expression and its impact on Hcy and H2S metabolism. Mice (C57BL/6) fed a HFD (60% kcal fat) for 5 weeks developed fatty liver. The mRNA and protein levels of CBS and CSE in the liver were significantly elevated in mice fed a HFD. Subsequently the metabolism of Hcy by CBS and CSE was increased in the liver and its level decreased in the circulation. Increased CBS and CSE expression also caused a significant elevation in H2S production in the liver. The level of lipid peroxides was elevated, indicating oxidative stress, while the level of total glutathione remained unchanged in the liver of HFD fed mice. Up-regulation of the transsulfutration pathway might play an adaptive role against oxidative stress by maintaining total glutathione levels in the liver.

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