title: Increased very low density lipoprotein secretion and gonadal fat mass in mice overexpressing liver DGAT1.
abstract: Acyl-CoA:diacylglycerol acyltransferases (DGATs) catalyze the last step in triglyceride (TG) synthesis. The genes for two DGAT enzymes, DGAT1 and DGAT2, have been identified. To examine the roles of liver DGAT1 and DGAT2 in TG synthesis and very low density lipoprotein (VLDL) secretion, liver DGAT1- and DGAT2-overexpressing mice were created by adenovirus-mediated gene transfection. DGAT1-overexpressing mice had markedly increased DGAT activity in the presence of the permeabilizing agent alamethicin. This suggests that DGAT1 possesses latent DGAT activity on the lumen of the endoplasmic reticulum. DGAT1-overexpressing mice showed increased VLDL secretion, resulting in increased gonadal (epididymal or parametrial) fat mass but not subcutaneous fat mass. The VLDL-mediated increase in gonadal fat mass might be due to the 4-fold greater expression of the VLDL receptor protein in gonadal fat than in subcutaneous fat. DGAT2-overexpressing mice had increased liver TG content, but VLDL secretion was not affected. These results indicate that DGAT1 but not DGAT2 has a role in VLDL synthesis and that increased plasma VLDL concentrations may promote obesity, whereas increased DGAT2 activity has a role in steatosis.
authors.affiliation: Division of Clinical Nutrition, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8636, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Eriko
authors.initials: E
authors.lastname: Sasaki
authors.forename: Chihaya
authors.initials: C
authors.lastname: Kakinuma
authors.forename: Takashi
authors.initials: T
authors.lastname: Yano
authors.forename: Shinji
authors.initials: S
authors.lastname: Miura
authors.forename: Osamu
authors.initials: O
authors.lastname: Ezaki
mesh_terms: D000217:Acyltransferases / Q000378:metabolism*; D000256:Adenoviridae / Q000235:genetics; D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000408:Alamethicin / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D001835:Body Weight; D018076:DNA, Complementary / Q000378:metabolism; D051048:Diacylglycerol O-Acyltransferase; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004822:Epididymis / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D015151:Immunoblotting; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000097:blood; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D008862:Microsomes, Liver / Q000378:metabolism; D017830:Octoxynol / Q000494:pharmacology; D009929:Organ Size; D010641:Phenotype; D012313:RNA / Q000737:chemistry; D013997:Time Factors; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D018076:DNA, Complementary; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D014475:Uncoupling Agents; D049452:Green Fluorescent Proteins; D000408:Alamethicin; D012313:RNA; D017830:Octoxynol; D000217:Acyltransferases; C494882:Dgat1 protein, mouse; D051048:Diacylglycerol O-Acyltransferase