Liver Low-density Lipoprotein Cholesterol Research Articles

Danggui Shaoyao powder improves hepatic lipid metabolism in atherosclerosis mice via PPARγ-LXRα-ABCA1 pathway regulation

ObjectiveTo observe the effects of Danggui Shaoyao powder (DSP) on hepatic lipid metabolism and further explore its mechanism of action by peroxisome proliferator-activated receptor (PPARγ)-liver X receptor (LXRα)-adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) pathway regulation. MethodsEight C57BL/6J male mice were selected as the control group, and 24 ApoE−/− male mice were randomly divided into the atherosclerosis model (AS) group, atorvastatin calcium (AC) group, and DSP group (n = 8 each group). To establish an AS model, ApoE−/− mice were fed a high-fat diet for 16 weeks. Pathologic changes in the aortic vasculature and liver were identified using Oil Red O staining. Triglyceride (TG), cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels were determined in the livers using a single-reagent GPO-PAP method. Fluorescence quantitative polymerase chain reaction and western blot were used to observe and evaluate the mRNA and protein expression of the PPARγ-LXRα-ABCA1 intermediates in the liver. ResultsAfter 16 weeks of a high-fat diet, ApoE−/− mice showed more Oil Red O staining in the aorta and liver compared to the CONT group. Compared to the AS group, the DSP and AC treatment reduced aortic plaque and hepatic lipid deposition to varying degrees. Furthermore, DSP significantly reduced the hepatic lipid area in ApoE−/− mice (P < .001) and decreased the levels of TG, TC, and LDL-C in liver (P < .001, P = .027, P < .001, respectively). DSP also significantly increased the levels of PPARγ, LXRα, ABCA1, and ABCG1 mRNA expression, as well as the PPARγ, LXRα, ABCA1, and ABCG1 protein expression in liver. ConclusionDSP improved hepatic lipid metabolism via PPARγ-LXRα-ABCA1 pathway modulation for AS treatment.

Selenium and vitamin B6 cosupplementation improves dyslipidemia and fatty liver syndrome by SIRT1/SREBP-1c pathway in hyperlipidemic Sprague-Dawley rats induced by high-fat diet

Previously, our group found that the dietary trace mineral element selenium and vitamin B6 (VitB6) alone was involved in lipid metabolism. However, the effects of selenium combined with VitB6 on hyperlipidemia and lipid metabolism have not been reported until now. We hypothesized that selenium and VitB6 cosupplementation would alleviate the hyperlipidemic and hepatic dysfunction and with minimum side effects in a Sprague-Dawley rat model of hyperlipidemia induced by a high-fat diet. Our results showed that selenium combined with VitB6 could improve dyslipidemia and displayed better in vivo hypocholesterolemic abilities at early intervention. Moreover, cosupplementation reduced atherogenic indexes (atherogenic index and atherogenic index of plasm) and the ratio of ApoB/ApoA1. The liver function index aspartate aminotransferase in serum was reduced, as was and total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol in liver. The intervention also increased the levels of ApoA1 in serum and high-density lipoprotein cholesterol of liver. In addition, the combination of selenium and VitB6 decreased liver lipid deposition and alleviated steatosis, reduced adipocyte size of white adipose tissue, increased the activities of hepatic lipase and total lipase and the hepatic 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGR) level, decreased the hepatic mRNA transcription of lipogenic and regulatory genes including Srebf1 and downstream fat synthesis-related enzymes (Acc and Fasn) and cholesterol synthesis speed limiting enzyme Hmgr, increased the mRNA abundance of Lcat and Cyp7a1, increased the protein expression of SIRT1 and PPARα, and up-regulated the protein expression of sterol regulatory element–binding protein 1c in the livers of hyperlipidemia rats. We first demonstrated that oral selenium and VitB6 cosupplementation exerted synergism in lowering blood and liver lipid profiles and antiatherosclerotic effects in hyperlipidemic rats by reducing endogenous cholesterol and lipid synthesis, enhancing the transport of cholesterol to hepatocytes and promoting fatty acid beta oxidation.

Efficacy of Kushen decoction on high-fat-diet-induced hyperlipidemia in rats.

To investigate the efficacy and underlying mechanisms of action of Kushen decoction on high-fat-diet-induced hyperlipidemia in rats using RNA-seq technology. The efficacy of a Kushen decoction, at a concentration of 1 mL/g of crude medicine prepared according to the method commonly used in clinical practice, was investigated on 24 specific pathogen-free male Sprague-Dawley rats. Liver tissues were compared using RNA-Seq technology. The differentially expressed genes were further investigated by real-time fluorescent quantitative polymerase chain reaction (qPCR and Western blot (WB). Serum triglycerides (TG), liver low-density lipoprotein cholesterol (LDL-C), body weight, body length, and Lee's index were significantly increased in the untreated hyperlipidemia-induced group (model) compared with the control group, whereas liver high-density lipoprotein cholesterol (HDL-C) was significantly decreased. Serum TG, liver LDL-C, bodyweight, and Lee's index were decreased in the high-dose Kushen decoction group (HDKS) compared with the model group, whereas liver HDL-C was significantly increased. Similarly, liver TG tended to decline in the HDKS group. Comparison of the gene expression profiles in the livers from different groups indicated that the Kushen decoction significantly affected metabolic pathways, PPAR signalling pathway, and circadian rhythm ( ≤ 0.05), with the genes ARNTL, PER3, and CLOCK being differentially expressed. qPCR and WB analysis confirmed the differential expression of the genes discovered by transcriptomics analysis. The Kushen decoction may achieve a lipid-lowering effect on hyperlipidemic rats by regulating metabolic pathways and the circadian rhythm pathway and in particular, their related genes ARNTL, PER3, and CLOCK.

Effect of taurine on lipid metabolism of broilers

To evaluate the effect of taurine supplements on broiler lipid metabolism, two hundred and forty 1-day-old Avian broilers were randomly divided into five groups, each group with three replicates for 21 days. The groups were fed basal diets with 0 (control group), 0.05%, 0.10%, 0.15% and 0.20% taurine, respectively. The results showed that dietary taurine of 0.15% increased apparent metabolisable energy and crude fat digestibility (P<0.05), enhanced the activity of lipase in pancreas and small intestine (P<0.05); compared to the control group, 0.15% taurine significantly decreased the content of serum total cholesterol (TC), triglycerides (TG), free fatty acids (FFA), glucose (GLU) and liver TG, FFA (P<0.05), increased the content of serum high density lipoprotein cholesterol (HDL-C) (P<0.05). A total of 0.20% taurine remarkably decreased the content of serum TC, low density lipoprotein cholesterol (LDL-C), GLU and liver LDL-C, FFA (P<0.05), increased the content of serum HDL-C, serum lipoprotein lipase and liver hepatic lipase activity (P < 0.05). Considering the physiological and biochemical indexes above, adding 0.15% taurine was optimal.

Influence of chronic stress on the compositions of hepatic cholesterol and triglyceride in male Wistar rats fed a high fat diet

We determined the influence of chronic stress (CS) on the compositions of hepatic cholesterol and triglyceride (TG) in rats fed a high fat diet (HFD). Male Wistar rats were fed either a standard diet or a HFD and half of the HFD fed rats were given CS (electric foot shock assisted with noise) for 8 weeks. Compared with the control group, the levels of hepatic total cholesterol (TC) and TG were significantly elevated in the HFD and HFD with chronic stress (HFD+CS) groups, and the more severe elevations of them were found in the HFD group. Inversely, the more severe elevations of hepatic water-soluble parts of TC and TG were found in the HFD+CS group, as the elevations of low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol in liver and serum, tumor necrosis factor-α, interleukin-1β and malondialdehyde in liver. Meanwhile, downregulated mRNA expressions of hepatic liver X receptor-α (LXR-α) and peroxisome proliferator-activated receptor-γ (PPAR-γ) were also more severe in the HFD+CS group. CS can aggravate the high levels of water-soluble compositions of hepatic TC and TG induced by HFD as it aggravates hepatic inflammation and oxidative stress; in spite of that, however, it cannot further promote hepatic lipidosis. This is consistent with the downregulated mRNA expressions of LXR-α and PPAR-γ.

Cholesterol metabolism regulation and antioxidant effect of platycodin D on hyperlipidemic emulsion-reduced rats

To study the potential mechanisms underlying cholesterol metabolism regulation and the antioxidant of platycodin D derived from Platycodon grandiflorum A.DC (PD), the male Wistar rats treated with hyperlipidemic emulsion diet for 2 weeks were fed with PD (10, 20 and 30 mg/kg body weight/d) and simvastatin (25 mg/kg body weight/d), respectively by gavage for 28 days. Different doses of PD depressed the serum and hepatic cholesterol, triglyceride and low-density lipoprotein cholesterol concentration, thereby increasing the liver low-density lipoprotein cholesterol receptor (LDL-r) protein content by immunohistochemical analysis and decreasing liver 3-Hydroxy-3-methyl glutaryl-CoA reductase (HMG-CoA-r) mRNA levels of hyperlipidemic emulsion induced rats. Cytochrome P450 7A1 (CYP7A1) mRNA expression and fecal bile acid levels were significantly higher in the PD groups as compared to the groups that have only hyperlipidemic emulsion. Simultaneously, treatment with PD also improved the serum and hepatic homogenate metabolic antioxidant status of hyperlipidemic emulsion induced rats. These findings suggested that metabolism regulation of PD on hyperlipidemic rats was caused, in part, by regulation of synthesis, influx and efflux of hepatic intracellular cholesterol via the key points LDL-r, HMG-CoA-r and CYP7A1, which consequently changed the organismal oxidation state. The study revealed that PD may offer a therapeutic potential for the treatment of hyperlipidemic via regulation of cholesterol metabolism. Key words: Platycodon grandiflorum, platycodin D cholesterol metabolism, antioxidation.

Tri-iodothyronine prevents the amiodarone-induced decrease in the expression of the liver low-density lipoprotein receptor gene.

Treatment with amiodarone, a potent antiarrhythmic drug, is associated with a dose-dependent increase in plasma cholesterol resulting from a decreased number of liver low-density lipoprotein (LDL) receptors. Similar changes occur in hypothyroidism, and it has been suggested that amiodarone acts via induction of a local 'hypothyroid-like' state in extrathyroidal tissues. The present study was designed to evaluate whether exogenous tri-iodothyronine (T3) could prevent the effects of amiodarone on LDL cholesterol. Rats were treated for 14 days with water, amiodarone 10 mg/100 g body weight (BW), or amiodarone and 2.5, 5 or 10 micrograms T3/100 g BW respectively. Relative to controls, amiodarone increased plasma LDL cholesterol by 31% and decreased liver LDL receptor mRNA by 56% and protein by 45%; liver T3 content was reduced by 21%. Addition of T3 to the treatment with amiodarone dose-dependently reversed all these changes, with a return to control values of plasma cholesterol and the number of liver LDL receptors, although LDL receptor mRNA remained slightly lower. Treatment of rats for 14 days with T3 alone (5 micrograms/100 g BW) decreased plasma LDL cholesterol by 19% and increased liver LDL receptor mRNA by 41%. In conclusion, T3 prevents the amiodarone-induced changes in plasma LDL cholesterol and liver LDL receptor gene expression. These findings suggest that the inhibitory effect of amiodarone on LDL receptor gene expression is mediated by T3-dependent pathways.