First Author | Lian J | Year | 2012 |
Journal | Circ Res | Volume | 111 |
Issue | 8 | Pages | 982-90 |
PubMed ID | 22872154 | Mgi Jnum | J:212633 |
Mgi Id | MGI:5581902 | Doi | 10.1161/CIRCRESAHA.112.267468 |
Citation | Lian J, et al. (2012) Ces3/TGH deficiency improves dyslipidemia and reduces atherosclerosis in Ldlr(-/-) mice. Circ Res 111(8):982-90 |
abstractText | RATIONALE: Carboxylesterase 3/triacylglycerol hydrolase (TGH) has been shown to participate in hepatic very low-density lipoprotein (VLDL) assembly. Deficiency of TGH in mice lowers plasma lipids and atherogenic lipoproteins without inducing hepatic steatosis. OBJECTIVE: To investigate the contribution of TGH to atherosclerotic lesion development in mice that lack low-density lipoprotein receptor (LDLR). METHODS AND RESULTS: Mice deficient in LDL receptor (Ldlr(-/-)) and mice lacking both TGH and LDLR (Tgh(-/-)/Ldlr(-/-)) were fed with a Western-type diet for 12 weeks. Analysis of Tgh(-/-)/Ldlr(-/-) plasma showed an atheroprotective lipoprotein profile with decreased cholesterol in the VLDL and the LDL fractions, concomitant with elevated high-density lipoprotein cholesterol. Significantly reduced plasma apolipoprotein B levels were also observed in Tgh(-/-)/Ldlr(-/-) mice. Consequently, Tgh(-/-)/Ldlr(-/-) mice presented with a significant reduction (54%, P<0.01) of the high-fat, high-cholesterol dieteninduced atherosclerotic plaques when compared with Tgh(+/+)/Ldlr(-/-) mice in the cross-sectional aortic root analysis. TGH deficiency did not further increase liver steatosis despite lowering plasma lipids, mainly due to reduced hepatic lipogenesis. The ameliorated dyslipidemia in Tgh(-/-)/Ldlr(-/-) mice was accompanied with significantly improved insulin sensitivity. CONCLUSIONS: Inhibition of TGH activity ameliorates atherosclerosis development and improves insulin sensitivity in Ldlr(-/-) mice. |