Betaine and Choline Improve Lipid Homeostasis in Obesity by Participation in Mitochondrial Oxidative Demethylation

We investigated the metabolic effects of betaine (Bet) supplementation on CTP:phosphoethanolamine cytidylyltransferase/Pcyt2 heterozygous mice (HET). HET received either no treatment or were allowed access to 1% Bet supplemented water for 8 weeks. As we previously showed with choline (Cho), Bet improved hypertriglyceridemia, and hepatic steatosis in HET. The protection from obesity associated with reduced hepatic steatosis and increased lipid breakdown in adipocytes was attributed to increased energy requirements for metabolism and elimination of supplemented Bet and Cho. (1)H-NMR-based profiling revealed metabolic changes caused by Bet and Cho supplementation. Cho increased the citric acid cycle intermediate succinic acid while reducing isoleucine, valine, threonine, and lysine. Bet increased α-ketoglutaric acid and did not stimulate catabolism of amino acids. Increased histidine and alanine are specific biomarkers for Bet treatment. Cho and Bet caused glycerol accumulation and reduced sarcosine, taurine, acetate, and β-hydroxybutyrate levels. These data provide new insights on how Cho and Bet supplementation can aid in treatment of obesity related disorders due to their positive effects on lipolysis, the citric acid cycle, and mitochondrial oxidative demethylation.