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 |
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Authors: | Teng Ya-Wen Ellis Jessica M Coleman Rosalind A Zeisel Steven H |
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Affiliation: | Department of Nutrition, School of Public Health, University of North Carolina, Chapel Hill, North Carolina 27599, USA. |
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Abstract: | 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. |
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Keywords: | Adipose Tissue Energy Metabolism Glucose Metabolism One-carbon Pool Phosphatidylcholine Betaine Betaine-Homocysteine S-Methyltransferase Choline |
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