Mouse Betaine-Homocysteine S-Methyltransferase Deficiency Reduces Body Fat via Increasing Energy Expenditure and Impairing Lipid Synthesis and Enhancing Glucose Oxidation in White Adipose Tissue

摘要

Betaine-homocysteine S-methyltransferase (BHMT) catalyzes the synthesis of methionine from homocysteine. In our initial report, we observed a reduced body weight in Bhmt^−/− mice. We initiated this study to investigate the potential role of BHMT in energy metabolism. Compared with the controls (Bhmt^+/+), Bhmt^−/− mice had less fat mass, smaller adipocytes, and better glucose and insulin sensitivities. Compared with the controls, Bhmt^−/− mice had increased energy expenditure, with no changes in food intake, fat uptake or absorption, or in locomotor activity. The reduced adiposity in Bhmt^−/− mice was not due to hyperthermogenesis. Bhmt^−/− mice failed to maintain a normal body temperature upon cold exposure because of limited fuel supplies. In vivo and ex vivo tests showed that Bhmt^−/− mice had normal lipolytic function. The rate of ¹⁴C-labeled fatty acid incorporated into [¹⁴C]triacylglycerol was the same in Bhmt^+/+ and Bhmt^−/− gonadal fat depots (GWAT), but it was 62% lower in Bhmt^−/− inguinal fat depots (IWAT) compared with that of Bhmt^+/+ mice. The rate of ¹⁴C-labeled fatty acid oxidation was the same in both GWAT and IWAT from Bhmt^+/+ and Bhmt^−/− mice. At basal level, Bhmt^−/− GWAT had the same [¹⁴C]glucose oxidation as did the controls. When stimulated with insulin, Bhmt^−/− GWAT oxidized 2.4-fold more glucose than did the controls. Compared with the controls, the rate of [¹⁴C]glucose oxidation was 2.4- and 1.8-fold higher, respectively, in Bhmt^−/− IWAT without or with insulin stimulus. Our results show for the first time a role for BHMT in energy homeostasis.