The CBS/CSE system: a potential therapeutic target in NAFLD?
Publication: Canadian Journal of Physiology and Pharmacology
17 November 2014
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a broad spectrum liver disorder diagnosed in patients without a history of alcohol abuse. NAFLD is growing at alarming rates worldwide. Its pathogenesis is complex and incompletely understood. The cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) system regulates homocysteine and cysteine metabolism and contributes to endogenous hydrogen sulfide (H2S) biosynthesis. This review summarizes our current understanding of the hepatic CBS/CSE system, and for the first time, positions this system as a potential therapeutic target in NAFLD. As will be discussed, the CBS/CSE system is highly expressed and active in the liver. Its dysregulation, presenting as alterations in circulating homocysteine and (or) H2S levels, has been reported in NAFLD patients and in NAFLD-associated co-morbidities such as obesity and type 2 diabetes. Intricate links between the CBS/CSE system and a number of metabolic and stress related molecular mediators have also emerged. Various dysfunctions in the hepatic CBS/CSE system have been reported in animal models representative of each NAFLD spectrum. It is anticipated that a newfound appreciation for the hepatic CBS/CSE system will emerge that will improve our understanding of NAFLD pathogenesis, and give rise to new prospective targets for management of this disorder.
Résumé
La stéatose hépatique non alcoolique (NAFLD, Non-alcoholic fatty liver disease) comprend un large spectre de maladies hépatiques diagnostiquées chez des patients sans historique d’abus d’alcool. La NAFLD croit à un rythme alarmant à travers le monde. Sa pathogenèse est complexe et incomplètement comprise. Le système constitué de la cystathionine-β-synthase (CBS) et la cystathionine-γ-lyase régule le métabolisme de l’homocystéine et de la cystéine et contribue à la biosynthèse de sulfure d’hydrogène (H2S) endogène. Cet article de revue résume ce qui est actuellement compris du système CBS/CSE hépatique et, pour la première fois, situe ce système comme cible thérapeutique potentielle de la NAFLD. Comme il sera discuté, le système CBS/CSE est exprimé fortement dans le foie où il est très actif. Sa dérégulation, qui se présente sous forme de modifications des niveaux circulants d’homocystéine et/ou de H2S, a été rapportée chez des patients souffrant de NAFLD et dans des comorbidités associées à la NAFLD comme l’obésité et le diabète de type 2. Des liens complexes entre le système CBS/CSE et un certain nombre de médiateurs moléculaires du métabolisme et du stress ont aussi émergé. Différentes dysfonctions du système CBS/CSE ont été rapportées dans des modèles animaux représentatifs de tout le spectre de NAFLD. On anticipe qu’une nouvelle appréciation du système CBS/CSE hépatique qui améliorera notre compréhension de la pathogenèse de la NAFLD émergera, et qu’elle donnera lieu à l’identification de nouvelles cibles prospectives pour contrôler cette maladie. [Traduit par la Rédaction]
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Published In
Canadian Journal of Physiology and Pharmacology
Volume 93 • Number 1 • January 2015
Pages: 1 - 11
History
Received: 9 October 2014
Accepted: 7 November 2014
Accepted manuscript online: 17 November 2014
Version of record online: 17 November 2014
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© 2014.
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SarnaLindsei K., SiowYaw L., and OKarmin. 2015. The CBS/CSE system: a potential therapeutic target in NAFLD?. Canadian Journal of Physiology and Pharmacology. 93(1): 1-11. https://doi.org/10.1139/cjpp-2014-0394