Inhibition of Lipogenesis by Betaine Involves Reduction of Homocysteine Via Upregulation of Betaine Homocysteine Methyltransferase

In this study, we investigated the underlying mechanism of AMPK activation provided by betaine using different cell lines. Betaine treatment enhanced phosphorylation of AMPK, SREBP-1c, and ACC in H4IIE, but not in HepG2 cell. Betaine homocysteine methyltransferase (BHMT) was induced and homocysteine concentration was decreased by betaine only in H4IIE cell. Homocysteine inhibited protein expression of pAMPK, pACC, pSREBP-1c, and pLKB1 in a dose-dependent manner, which was all prevented by betaine treatment. BHMT protein expression was also inhibited by homocysteine and betaine reversed its inhibition in H4IIE cell. Treatment of hydroxylamine, a cystathionine β synthase (CβS) inhibitor, resulted in a significant increment of homocysteine in HepG2 cell. Phosphorylation of AMPK, ACC, and SREBP-1c was significantly reduced by hydroxylamine. Metformin treatment to HepG2 cell increased phosphorylation of AMPK, ACC, and SREBP-1c, which was inhibited by homocysteine. Taken together, the results indicate that the elevation of homocysteine in hepatocyte is responsible for inactivation of the AMPK pathway. It is strongly suggested that anti-lipogenic activity of betaine is associated with depletion of homocysteine via upregulation of BHMT.

Source: Advances in Nutrition - January 15, 2016 Category: Nutrition Authors: Kim, Y. C., Ahn, C., Jun, D. Tags: Disease Prevention, Progression, and Treatment Source Type: research