Liver X receptor agonist T0901317 reduces atherosclerotic lesions in <Emphasis Type="Italic">apoE</Emphasis><Superscript>-/-</Superscript> mice by up-regulating <Emphasis Type="Italic">NPC1</Emphasis> expression

In this study, we studied the effect of liver X receptor (LXR) agonist T0901317 on Niemann-Pick C1 protein (NPC1) expression in apoE ^-/- mice. Male apoE ^-/- mice were randomized into 4 groups, baseline group (n=10), control group (n=14), treatment group (n=14) and prevention group (n=14). All of the mice were fed with a high-fat/high-cholesterol (HFHC) diet containing 15% fat and 0.25% cholesterol. The baseline group treated with vehicle was sacrificed after 8 weeks of the diet. The control group and the prevention group were treated with either vehicle or T0901317 daily by oral gavage for 14 weeks. The treatment group was treated with vehicle for 8 weeks, and then was treated with the agonist T0901317 for additional 6 weeks. Gene and protein expression was analyzed by real-time quantitative PCR, immunohistochemistry and Western blotting, respectively. Plasma lipid concentrations were measured by commercially enzymatic methods. We used RNA interference technology to silence NPC1 gene expression in THP-1 macrophage-derived foam cells and then detected the effect of LXR agonist T0901317 on cholesterol efflux. Plasma triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and apoA-I concentrations were markedly increased in T0901317-treated groups. T0901317 treatment reduced the aortic atherosclerotic lesion area by 64.2% in the prevention group and 58.3% in the treatment group. LXR agonist treatment increased NPC1 mRNA expression and protein levels in the small intestine, liver and aorta of apoE ^-/- mice. Compared with the normal cells, cholesterol efflux of siRNA THP-1 macrophage-derived foam cells was significantly decreased, whereas cholesterol efflux of LXR agonist T0901317-treated THP-1 macrophage-derived foam cells was significantly increased. Our results suggest that LXR agonist T0901317 inhibits atherosclerosis development in apoE ^-/- mice, which is related to up-regulating NPC1 expression.     

Liver X receptor agonist T0901317 reduces athero-sclerotic lesions in apoE-/- mice by up-regulating NPC1 expression

In this study, we studied the effect of liver X receptor (LXR) agonist T0901317 on Niemann-Pick C1 protein (NPC1) expression in apoE-/- mice. Male apoE-/- mice were randomized into 4 groups, baseline group (n=10), control group (n=14), treatment group (n=14) and prevention group (n=14). All of the mice were fed with a high-fat/high-cholesterol (HFHC) diet containing 15% fat and 0.25% cholesterol. The baseline group treated with vehicle was sacrificed after 8 weeks of the diet. The control group and the prevention group were treated with either vehicle or T0901317 daily by oral gavage for 14 weeks. The treatment group was treated with vehicle for 8 weeks, and then was treated with the agonist T0901317 for additional 6 weeks. Gene and protein expression was analyzed by real-time quantitative PCR, immunohistochemistry and Western blotting, respectively. Plasma lipid concentrations were measured by commercially enzymatic methods. We used RNA interference technology to silence NPC1 gene expression in THP-1 macrophage-derived foam cells and then detected the effect of LXR agonist T0901317 on cholesterol efflux. Plasma triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and apoA-I concentrations were markedly increased in T0901317-treated groups. T0901317 treatment reduced the aortic atherosclerotic lesion area by 64.2% in the prevention group and 58.3% in the treatment group. LXR agonist treatment increased NPC1 mRNA expression and protein levels in the small intestine, liver and aorta of apoE-/- mice. Compared with the normal cells, cholesterol efflux of siRNA THP-1 macrophage-derived foam cells was significantly decreased, whereas cholesterol efflux of LXR agonist T0901317-treated THP-1 macrophage-derived foam cells was significantly increased. Our results suggest that LXR agonist T0901317 inhibits atherosclerosis development in apoE-/- mice, which is related to up-regulating NPC1 expression.     

Effects of folic acid on growth performance,ruminal fermentation,nutrient digestibility and urinary excretion of purine derivatives in post-weaned dairy calves

This study evaluated the effects of folic acid (FA) supplementation on growth performance, ruminal fermentation, nutrient digestibility and urinary purine derivatives (PD) excretion in dairy calves. Forty-eight Chinese Holstein male dairy calves at 60 ± 3.2 d of age and 89 ± 5.9 kg body weight (mean ± standard error) were assigned to one of four groups in a randomised block design. Calves in control group were fed basal diet, calves in low FA, medium FA and high FA groups with 3.6, 7.2 and 10.8 mg FA per kg basal diet, respectively. The dietary corn silage to concentrate ratio was 50:50 (dry matter [DM] basis). DM intake and average daily gain (ADG) quadratically increased, and feed conversion ratio quadratically decreased with increasing FA supplementation. Ruminal pH linearly decreased, whereas total volatile fatty acids quadratically increased. The unchanged acetate-to-propionate ratio was due to the similar change in acetate and propionate concentration. Ammonia N content quadratically decreased. Digestibility of DM, organic matter, crude protein, ether extract, neutral detergent fibre and acid detergent fibre linearly increased. Activities of carboxymethyl cellulase, cellobiase, xylanase and pectinase linearly increased, but α-amylase and protease quadratically increased. Abundance of Ruminococcus albus, Ruminococcus flavefaciens and Fibrobacter succinogenes linearly increased, but Butyrivibrio fibrisolvens and Prevotella ruminicola quadratically increased. Urinary total PD excretion quadratically increased. The results indicated that FA supplementation increased ADG, ruminal fermentation and nutrient digestibility with promoted ruminal microbial growth and enzyme activity, and the optimum dose was 7.2 mg FA per kg basal diet for calves.