| First Author | Bordoloi J | Year | 2019 |
| Journal | J Nutr Biochem | Volume | 70 |
| Pages | 174-184 | PubMed ID | 31226525 |
| Mgi Jnum | J:297929 | Mgi Id | MGI:6479418 |
| Doi | 10.1016/j.jnutbio.2019.05.006 | Citation | Bordoloi J, et al. (2019) Gamma-glutamyl carboxylated Gas6 mediates the beneficial effect of vitamin K on lowering hyperlipidemia via regulating the AMPK/SREBP1/PPARalpha signaling cascade of lipid metabolism. J Nutr Biochem 70:174-184 |
| abstractText | The present study for the first time aims to examine the hypothesis that circulating gamma-glutamyl carboxylated growth arrest specific protein 6 (Gla-Gas6) deficiency may be associated with hyperlipidemia and vitamin K (VK) supplementation may ameliorate the impaired lipid homeostasis via activating Gas6 protein. Subjects with hyperlipidemia (n=22) and age-matched healthy controls (n=19) were included in this study. Results showed that plasma levels of Gla-Gas6 protein and VK were significantly lower in hyperlipidemic subjects compared to control. Moreover, Gla-Gas6 levels were significantly and positively correlated with VK (P=.034, r=0.452) and negatively with triglyceride (P=.022, r=-0.485) and total cholesterol (P=.043, r=-0.435) in hyperlipidemic subjects, which suggest that VK supplementation may have a positive effect in activating Gas6 protein and thereby reducing the aberrant plasma lipid levels. Further studies with high-fat diet (HFD)-fed animal model of hyperlipidemia demonstrated that VK supplementation (5 mug/kg body weight, 8 weeks) reduced the plasma lipid levels, stimulated both the plasma levels and the hepatic protein expression of Gla-Gas6 protein, and regulated the AMPK/SREBP1/PPARalpha signaling pathways of hepatic lipid metabolism in HFD-fed mice. Moreover, by using palmitic acid (PA, 0.75 mM)-treated both control and GGCX knockdown hepatocytes, this study dissected the direct role of Gla-Gas6 in mediating the positive effect of VK on preventing the PA-induced impaired hepatic lipid metabolism via regulating AMPK/SREBP1/PPARalpha pathways. Combining all, the present study demonstrated the beneficial effect of VK supplementation in preventing the impaired lipid homeostasis via activating VK-dependent Gas6 protein. |
