title: 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.
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.
authors.affiliation: Department of Nutrition, School of Public Health, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Teng
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Ellis
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Coleman
authors.forename: Steven H
authors.initials: SH
authors.lastname: Zeisel
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D050940:Betaine-Homocysteine S-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D008055:Lipids / Q000096:biosynthesis*; D008066:Lipolysis / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction
chemical_list: D008055:Lipids; D050940:Betaine-Homocysteine S-Methyltransferase; C494549:Bhmt protein, mouse; D005947:Glucose