title: Sterol regulatory element binding protein 2 overexpression is associated with reduced adipogenesis and ectopic fat accumulation in transgenic spontaneously hypertensive rats.
abstract: It has been reported that the major function of the sterol regulatory element binding protein 2 (SREBP-2) is to activate preferentially cholesterol biosynthesis in liver and adipose tissue rather than fatty acid synthesis. In the current study, we analyzed the effects of overexpression of human dominant-positive SREBP-2 transgene under control of PEPCK promoter in the spontaneously hypertensive rat (SHR) on lipid and glucose metabolism. Transgenic overexpression of SREBP-2 was associated with significantly higher hepatic triglycerides (20.4+/-0.9 vs. 17.0+/-0.05 micromol/g, P<0.05) but not cholesterol (10.6+/-0.4 vs. 10.9+/-0.4 micromol/g) and decreased relative weight of epididymal fat pad (0.73+/-0.03 vs. 0.83+/-0.03, P<0.05). In addition, muscle triglyceride (15.8+/-3.7 vs. 8.5+/-1.2 micromol/g, P<0.001) and cholesterol (3.6+/-0.5 vs. 2.1+/-0.1 micromol/g, P<0.05) concentrations were significantly increased in transgenic rats when compared to SHR controls. Ectopic fat accumulation was associated with significantly increased serum glucose levels (6.4+/-0.1 vs. 5.9+/-0.1 mmol/l, P<0.005) and reduced insulin levels (1.78+/-0.33 vs. 2.73+/-0.37 nmol/l, P<0.05) in transgenic rats. These results provide evidence for important role of SREBP-2 in regulation of lipid and glucose metabolism.
authors.affiliation: Institute of Physiology Academy of Sciences of the Czech Republic, Prague, Czech Republic. pravenec@biomed.cas.cz.
authors.forename: V
authors.initials: V
authors.lastname: Landa
authors.forename: V
authors.initials: V
authors.lastname: Zídek
authors.forename: P
authors.initials: P
authors.lastname: Mlejnek
authors.forename: M
authors.initials: M
authors.lastname: Šimáková
authors.forename: J
authors.initials: J
authors.lastname: Šilhavý
authors.forename: J
authors.initials: J
authors.lastname: Trnovská
authors.forename: L
authors.initials: L
authors.lastname: Kazdová
authors.forename: M
authors.initials: M
authors.lastname: Pravenec
mesh_terms: D050156:Adipogenesis; D000273:Adipose Tissue / Q000378:metabolism* / Q000503:physiopathology; D050154:Adiposity; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008099:Liver / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics; D011401:Promoter Regions, Genetic; D011918:Rats, Inbred SHR; D055647:Rats, Transgenic; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; C497390:SREBF2 protein, human; D051782:Sterol Regulatory Element Binding Protein 2; D014280:Triglycerides; D002784:Cholesterol; C582554:Pck1 protein, rat; D010729:Phosphoenolpyruvate Carboxykinase (GTP)