I didn't know Homocysteine could ever be a benefit.
Hepatol Res. 2018 Jul 26. doi: 10.1111/hepr.13234.
Minami S1, Miura K1,2, Ishioka M1, Morimoto N2, Isoda N2, Yamamoto H2, Iijima K1.
AIM:
High concentrations of homocysteine are believed to induce lipid synthesis and cell injury through endoplasmic reticulum (ER) stress in metabolic syndrome. However, homocysteine may be used to improve steatohepatitis induced by choline deficiency, in which methyl donors are decreased. The aim of the present study was to clarify the role of the physiological concentration of homocysteine in the development of steatohepatitis induced by choline deficiency.
METHODS:
Wild-type (WT) mice were fed a choline-deficient amino acid-defined (CDAA) diet with or without homocysteine supplementation for 24 weeks. Liver cells isolated from mice were exposed to homocysteine under choline-deficient conditions.
RESULTS:
WT mice fed the CDAA diet exhibited steatohepatitis with increased ER stress and decreased S-Adenosylmethionine (SAM), a methyl donor. Homocysteine supplementation reduced ER stress and restored hepatic SAM, leading to the improvement of steatohepatitis. in vitro experiments using primary cultured hepatocytes, the physiological concentration of homocysteine decreased the lipid accumulation and ER stress induced by the choline-deficient conditions. On the other hand, hepatocyte death was not induced by at a physiological concentration of homocysteine or in choline-deficient medium. Interestingly, tumor necrosis factor (TNF) α promoted hepatocyte death under choline-deficient conditions, which was suppressed by homocysteine supplementation. Hepatic macrophages increased the production of TNFα under choline-deficient condition whereas supplementation of SAM reduced the TNFα production.
CONCLUSIONS:
Homocysteine supplementation ameliorates steatohepatitis by reducing ER stress and increasing SAM in mice fed a CDAA diet. These results were opposite to those of previous reports, which showed that homocysteine induced cell injury.
PMID: 30048033