Homocysteine-induced endoplasmic reticulum stress activates FGF21 via CREBH, resulting in browning and atrophy of white adipose tissue in Bhmt knockout mice

Betaine-homocysteine methyltransferase (BHMT) catalyzes the transfer of methyl-groups from betaine to homocysteine (Hcy) producing methionine and dimethylgycine. In this work, we characterize Bhmt wildtype (WT) and knockout (KO) mice that were fully backcrossed to a C57Bl6/J background. Consistent with our previous findings, Bhmt KO mice had decreased body weight, fat mass and adipose tissue weight compared to WT. Histological analyses and gene expression profiling indicate that adipose browning was activated in KO mice and contributed to the adipose atrophy observed. BHMT is not expressed in adipose tissue but is abundant in liver, thus, a signal must be originating from the liver that modulates adipose tissue. We found that, in Bhmt KO mice, homocysteine-induced endoplasmic reticulum (ER) stress, with activation of hepatic transcription factor cyclin AMP response element binding protein (CREBH), mediated an increase in hepatic and plasma concentrations of fibroblast growth factor 21 (FGF21), which is known to induce adipose browning. CREBH binds to the promoter regions of FGF21 to activate its expression. Taken together, our data indicate that deletion of a single gene in one-carbon metabolism modifies adipose biology and energy metabolism. It would be interesting to determine whether people with functional polymorphisms in BHMT exhibit a similar adipose atrophy phenotype.

Exploring effects of betaine-homocysteine methyltransferase (BHMT) gene polymorphisms on fatty acid traits and cholesterol in sheep

This study was aimed to explore the effects of Betaine-Homocysteine Methyltransferase (BHMT) gene polymorphisms on fatty acid traits and cholesterol in lambs. This study used a total of 147 blood samples for genotyping including 19 Javanese Fat-Tailed (JFT), 16 Javanese Thin-Tailed (JTT), 41 Composite Garut (CG), 35 Compass Agrinak (CA) and 36 Barbados Black Belly Cross (BC). A total of 61 rams as representative from five breed of sheep were selected for association study. Identification of BHMT single nucleotide polymorphisms was analyzed by PCR-RFLP method. Association of BHMT genotypes with fatty acid traits and cholesterol was performed by T-TEST. BHMT genotyping resulted into three genotypes (CC, CT and TT). Gene frequency of BHMT (g. 9947372 C>T) was in Hardy-Weinberg Equilibrium, excluding Javanese Fat-Tailed sheep. Association of BHMT genotypes with fatty acid traits resulted into a significant association (P<0.05) with C14:1, C17:1 and C18:0 fatty acids but not with cholesterol in sheep. SNP g. 9947372 (C>T) of BHMT gene might be a useful marker for selecting and producing sheep meat with desirable fatty acids.

Alleviation of paraquat-induced oxidative lung injury by betaineviaregulation of sulfur-containing amino acid metabolism despite the lack of betaine-homocysteine methyltransferase (BHMT) in the lung

Betaine regulates sulfur-containing amino acid metabolism in the lung despite the lack of BHMT and increases pulmonary antioxidant capacity.

Betaine alleviates hepatic lipid accumulation via enhancing hepatic lipid export and fatty acid oxidation in rats fed with a high-fat diet - CORRIGENDUM

In the abstract, these sentences (page 1, line 5) should be: ‘Additionally, hepatic betaine–homocysteine methyltransferase concentration as well as its mRNA abundance and lecithin level were found increased (P<0·05) by betaine supplementation in both basal diet-fed rats and high-fat diet-fed rats. Betaine administration in high-fat diet-fed rats exhibited a higher (P<0·05) concentration of hepatic carnitine palmitoyltransferase 1 (CPT1) comparedwith high-fat diet-fed rats.’