AIMS/HYPOTHESIS: The aim of this study was to investigate the effects of liver X receptor (LXR) activation on lipid metabolism and insulin action in human skeletal muscle cells prepared from control subjects and from patients with type 2 diabetes. SUBJECTS AND METHODS: Cultured myotubes were obtained from muscle biopsies of 11 lean, healthy control subjects and ten patients with type 2 diabetes. The mRNA levels of LXR isoforms and lipogenic genes were estimated by RT-quantitative PCR, and the effects of LXR agonists on insulin action were evaluated by assays of protein kinase B serine 473 phosphorylation and glycogen synthesis. RESULTS: Both LXRalpha and LXRbeta were expressed in human skeletal muscle and adipose tissue and there was no difference in their mRNA abundance in tissues from patients with type 2 diabetes compared with control subjects. In cultured muscle cells, LXR activation by T0901317 strongly increased expression of the genes encoding lipogenic enzymes, including sterol regulatory element binding protein 1c, fatty acid synthase and stearoyl-CoA desaturase 1, and also promoted triglyceride accumulation in the presence of a high glucose concentration. Importantly, these effects on lipid metabolism did not affect protein kinase B activation by insulin. Furthermore, LXR agonists did not modify insulin action in muscle cells from patients with type 2 diabetes. CONCLUSIONS/ INTERPRETATION: These data suggest that LXR agonists may lead to increased utilisation of lipids and glucose in muscle cells without affecting the mechanism of action of insulin. However, the long-term consequences of triglyceride accumulation in muscle should be evaluated before the development of effective LXR-based therapeutic agents.
AIMS/HYPOTHESIS: The aim of this study was to investigate the effects of liver X receptor (LXR) activation on lipid metabolism and insulin action in human skeletal muscle cells prepared from control subjects and from patients with type 2 diabetes. SUBJECTS AND METHODS: Cultured myotubes were obtained from muscle biopsies of 11 lean, healthy control subjects and ten patients with type 2 diabetes. The mRNA levels of LXR isoforms and lipogenic genes were estimated by RT-quantitative PCR, and the effects of LXR agonists on insulin action were evaluated by assays of protein kinase B serine 473 phosphorylation and glycogen synthesis. RESULTS: Both LXRalpha and LXRbeta were expressed in human skeletal muscle and adipose tissue and there was no difference in their mRNA abundance in tissues from patients with type 2 diabetes compared with control subjects. In cultured muscle cells, LXR activation by T0901317 strongly increased expression of the genes encoding lipogenic enzymes, including sterol regulatory element binding protein 1c, fatty acid synthase and stearoyl-CoA desaturase 1, and also promoted triglyceride accumulation in the presence of a high glucose concentration. Importantly, these effects on lipid metabolism did not affect protein kinase B activation by insulin. Furthermore, LXR agonists did not modify insulin action in muscle cells from patients with type 2 diabetes. CONCLUSIONS/ INTERPRETATION: These data suggest that LXR agonists may lead to increased utilisation of lipids and glucose in muscle cells without affecting the mechanism of action of insulin. However, the long-term consequences of triglyceride accumulation in muscle should be evaluated before the development of effective LXR-based therapeutic agents.
Authors: Laura L Listenberger; Xianlin Han; Sarah E Lewis; Sylvaine Cases; Robert V Farese; Daniel S Ory; Jean E Schaffer Journal: Proc Natl Acad Sci U S A Date: 2003-03-10 Impact factor: 11.205
Authors: K D Whitney; M A Watson; B Goodwin; C M Galardi; J M Maglich; J G Wilson; T M Willson; J L Collins; S A Kliewer Journal: J Biol Chem Date: 2001-08-23 Impact factor: 5.157
Authors: Bryan A Laffitte; Lily C Chao; Jing Li; Robert Walczak; Sarah Hummasti; Sean B Joseph; Antonio Castrillo; Damien C Wilpitz; David J Mangelsdorf; Jon L Collins; Enrique Saez; Peter Tontonoz Journal: Proc Natl Acad Sci U S A Date: 2003-04-15 Impact factor: 11.205
Authors: L Al-Khalili; A V Chibalin; K Kannisto; B B Zhang; J Permert; G D Holman; E Ehrenborg; V D H Ding; J R Zierath; A Krook Journal: Cell Mol Life Sci Date: 2003-05 Impact factor: 9.261
Authors: D Rebourcet; F Odet; A Vérot; E Combe; E Meugnier; S Pesenti; P Leduque; H Déchaud; S Magre; B Le Magueresse-Battistoni Journal: Int J Androl Date: 2009-01-03