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Teng, Y.W. et al.

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.

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 (14)C-labeled fatty acid incorporated into [(14)C]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 (14)C-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 [(14)C]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 [(14)C]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.[1]

References

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. Teng, Y.W., Ellis, J.M., Coleman, R.A., Zeisel, S.H. J. Biol. Chem. (2012) [Pubmed]

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