- Email: [email protected]
Abstract: 1104 FUNCTION OF MUSCULAR VERY LOW-DENSITY LIPOPROTEIN RECEPTOR IN UPTAKE OF TRIGLYCERIDE-RICH LIPOPROTEIN AND CONTROLLING PLASMA TRIGLYCERIDE CONCENTRATION
Workshop VI-7 - Lipoprotein Metabolism: Lipoprotein Receptors Abstract: 1104 Citation: Atherosclerosis Supplement 2009, Vol. 10, Issue 2
FUNCTION OF MUSCULAR VERY LOW-DENSITY LIPOPROTEIN RECEPTOR IN UPTAKE OF TRIGLYCERIDE-RICH LIPOPROTEIN AND CONTROLLING PLASMA TRIGLYCERIDE CONCENTRATION Y Zenimaru, S Takahashi, T Kimura, M Imagawa, J Suzuki, I Miyamori Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui Objectives: Very low-density lipoprotein receptor (VLDLr) is exclusively expressed in heart, muscle and adipose tissue, which are active in fatty acid metabolism. To explore function of VLDLr in energy metabolism, its expression and regulation were investigated in vitro and in vivo. Methods: Rat L6 myoblasts (L6), rat smooth muscle cells (SMC), and rat primary skeletal myoblasts (SkM) were cultured in glucose-deprived conditions. Protein and mRNA expression of VLDLr, LDLr, lipoprotein lipase (LPL), and AMPK were analyzed by Western blotting or qRTPCR. The uptake of lipoproteins was analyzed by DiI- or 125I-labeled lipoproteins. Plasma triglyceride (TG) level was measured in LDLr/VLDLr double knockout mice (DKO) and LDLr-KO mice (LKO). Results: 1) Both protein and mRNA expression of VLDLr were increased with glucose deprivation in L6, SMC and SkM, whereas mRNA expression of LPL and LDLr were not altered. 2) AMPK phosphorylation was increased after 3 h glucose deprivation, followed by increased VLDLr protein expression after 6 h of glucose deprivation in L6. 3) Insulin also increased VLDLr protein expression in a dose-dependent manner. 4) The uptake of ȕ-VLDL was increased with glucose deprivation in L6, while LDL uptake was not altered. 5) TG level was elevated in DKO in both fed and fasted state compared to that in LKO. Conclusions: VLDLr-mediated uptake of TG-rich lipoprotein compensates for glucose deprivation through AMPK activation in muscle cells, and this pathway plays an important role in regulating plasma TG level in vivo. Funding: Supported by a grant from Japan Society for the Promotion of Science.
FUNCTION OF MUSCULAR VERY LOW-DENSITY LIPOPROTEIN RECEPTOR IN UPTAKE OF TRIGLYCERIDE-RICH LIPOPROTEIN AND CONTROLLING PLASMA TRIGLYCERIDE CONCENTRATION Y Zenimaru, S Takahashi, T Kimura, M Imagawa, J Suzuki, I Miyamori Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui Objectives: Very low-density lipoprotein receptor (VLDLr) is exclusively expressed in heart, muscle and adipose tissue, which are active in fatty acid metabolism. To explore function of VLDLr in energy metabolism, its expression and regulation were investigated in vitro and in vivo. Methods: Rat L6 myoblasts (L6), rat smooth muscle cells (SMC), and rat primary skeletal myoblasts (SkM) were cultured in glucose-deprived conditions. Protein and mRNA expression of VLDLr, LDLr, lipoprotein lipase (LPL), and AMPK were analyzed by Western blotting or qRTPCR. The uptake of lipoproteins was analyzed by DiI- or 125I-labeled lipoproteins. Plasma triglyceride (TG) level was measured in LDLr/VLDLr double knockout mice (DKO) and LDLr-KO mice (LKO). Results: 1) Both protein and mRNA expression of VLDLr were increased with glucose deprivation in L6, SMC and SkM, whereas mRNA expression of LPL and LDLr were not altered. 2) AMPK phosphorylation was increased after 3 h glucose deprivation, followed by increased VLDLr protein expression after 6 h of glucose deprivation in L6. 3) Insulin also increased VLDLr protein expression in a dose-dependent manner. 4) The uptake of ȕ-VLDL was increased with glucose deprivation in L6, while LDL uptake was not altered. 5) TG level was elevated in DKO in both fed and fasted state compared to that in LKO. Conclusions: VLDLr-mediated uptake of TG-rich lipoprotein compensates for glucose deprivation through AMPK activation in muscle cells, and this pathway plays an important role in regulating plasma TG level in vivo. Funding: Supported by a grant from Japan Society for the Promotion of Science.