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Excessive lipid deposition, liver injury, and insulin resistance are hallmarks in the development and progression of nonalcoholic fatty liver disease (NAFLD). Liver X receptor (LXR) is a transcriptional regulator, and its two cell subtypes, LXRα and LXRβ, play a key role in regulating cholesterol metabolism, inducing anti-inflammation, and reducing insulin resistance. This article reviews the structure and function of LXR and its association with the pathogenesis of NAFLD, in order to provide new ideas and methods for the prevention and treatment of NAFLD.
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Objective:To observe the effect of herbal cake-partitioned moxibustion on liver X receptor alpha (LXRα) in rabbits with atherosclerosis.Methods:Thirty-six male New Zealand rabbits were randomly divided into a normal group,a model group,a herbal cake-partitioned moxibustion group and a simvastatin group according to the random number table method,with 9 rabbits in each group.Rabbits in the model group,the herbal cake-partitioned moxibustion group and the simvastatin group were modeled by high fat feeding method which took 12 weeks.After verification of the successful model,rabbits in the normal group were not treated,in the model group were bundled,in the herbal cake-partitioned moxibustion group were treated with herbal cake-partitioned moxibustion,and those in the simvastatin group were treated with simvastatin,all for a total of 4 weeks.At the end of the experiment,the aorta and liver were observed for pathological changes;serum and liver were used to detect lipid levels;Western blot (WB) and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect LXRα protein and mRNA expression levels,respectively.Results:Compared with the normal group,the structure of aorta was disordered,the wall was rough and thick,the intima was unsmooth,and the vascular smooth muscle cells were arranged closely and disorderly in the model group,which was consistent with the characteristics of the rabbit model of aortic atherosclerosis.Compared with the model group,the aortic structure was clear,the degree of hepatocyte degeneration was reduced,the serum total cholesterol and low-density lipoprotein levels were significantly decreased (all P＜0.01),the high-density lipoprotein level was elevated (P＜0.01),and the total liver cholesterol was decreased significantly (P＜0.01) in the rabbits of the herbal cake-partitioned moxibustion group and the simvastatin group;compared with the model group,the protein (P＜0.01 or P＜0.05) and mRNA (P＜0.01) expressions of rabbit LXRα in the herbal cake-partitioned moxibustion group and the simvastatin group were increased.Conclusion:Herbal cake-partitioned moxibustion can improve the aortic and hepatic lesions,regulate blood lipid and liver lipid levels,increase the expression of liver cholesterol reverse transport nuclear receptor LXRα,promote reverse cholesterol transport in the rabbits with aortic atherosclerosis,therefore produces an antiatherogenic effect.
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Objective To investigate the protective effects and the possible mechanisms of GW3965, a liver X receptors (LXRs) agonist, in mice with PQ-induced acute lung injury. Methods A total of 40 male c57BL/6J mice were randomly(random number) divided into four groups. In control group, mice were intra-peritoneally injected with 0.1 mL normal saline solution twice at an interval of 10 min. In paraquat poisoning group, mice were intra-peritoneally injected with paraquat in a dose of 28 mg/kg and 0.1 mL normal saline solution 10 min later. In low dose GW3965 treatment group, mice were intra-peritoneally injected with GW3965 in a dose of 10 mg/kg 10 min after PQ administration. In high dose GW3965 treatment group, mice were intra-peritoneally injected with GW3965 in a dose of 50 mg/kg at 10 min after PQ administration. The mice were sacrifi ced at 72 h after PQ administration to collect lung tissues and blood specimens. Malonaldehyde(MDA) levels in blood were measured by thiobarbituric acid (TBA) method, and IL-1β and TNF-α levels in blood and lung tissues were measured using ELISA assay. Lung tissues were collected to determine the wet-to-dry (W/D) ratios ,histopathology changes by HE staining , and the levels of p38 MAPK, Bax and Bcl-2 were detected by Western blot as well as cell apoptosis by TUNEL. Multiple groups were compared with One-way ANOVA and pairwise comparison among groups were made by least signifi cance difference (LSD) determination. Results Compared with the control group, the PQ group had more severe lung injury, greater wet/dry weight ratio, higher MDA level in blood, higher IL-1β and TNF-α level in blood and lung tissues, higher expression of p38 MAPK, greater Bax/Bcl-2 ratio and greater numbers of cell apoptosis in lung tissues(P<0.05). GW3965 treatment attenuated all these changes(P<0.05), and the effect of GW3965 in high dose treatment group was more remarkable(P<0.05). Conclusion GW3965 significantly attenuates PQ-induced acute lung injury in mice. This effect may be associated with the inhibition of p38 MAPK signal pathway.
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Aim To investigate whether liver X recep- tors attenuate high glucose-induced apoptosis in H9C2 cells through inhibiting nuclear factor-NF-κB.Methods The lentiviral vector of LXRs was constructed and H9C2 cells cultured in high glucose were infected.The H9C2 cells were divided into 6 groups:control group (5.5 mmol·L -1 glucose),mannitol group(5.5 mmol ·L -1 glucose +27.5 mmol·L -1 mannitol),high glu-cose group(33 mmol·L -1 glucose),green fluorescent protein(GFP)group LXRαgroup,and LXRβgroup. The inhibition rate of H9C2 cells,the mRNA of Bax, Bcl-2,the protein content of NF-κB,Bax,Bcl-2, cleaved caspase-3,and the cell apoptosis were com-pared among these groups.Results LXRs overexpres-sion significantly attenuated high glucose-induced in-crease in Bax NF-κB,cleaved caspase-3 and cell ap-optosis(P <0.05),and increased high glucose-induced decrease in Bcl-2.Conclusion Liver X receptors at-tenuate high glucose-induced apoptosis in H9C2 cells through NF-κB signaling pathway.
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The liver X receptor(LXR) is one of the nuclear receptors related to metabolic syndrome.LXR plays an important role in the balance of cholesterol and lipid metabolism.LXR has been found to increase the utilization of glucose,decrease the insulin resistance,and simultaneously has an adverse effect in islet β cell.LXR influences fat cell differentiation and reduces expression of the obese gene then cause obesity.It also participates the development of non-alcoholic fatty liver and control the atherosclerosis.LXR is involved in inflammatory responses in macrophages and lymphocytes.The ability of LXR to integrate metabolic and inflammatory signaling makes it particularly attractive target for intervention in human metabolic diseases.In this review,we summarize the studies of LXR,clarify the LXR in the prospects for the treatment of metabolic syndrome.
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Objective To observe the fatty deposition in thapsigargin-induced endoplasmic reticulum stress model in hepatocytes and to discuss the possible mechanism. Methods Hepatocytes (L02 cell and HepG2 cell line) were divided into control group and experimental group (treated with 1 μmol/L thapsigargin). Fatty deposition in the hepatocytes was observed by biochemical assay and oil red O staining. Real-time PCR was used to test the expression of SREBP-1c and LXRs mRNA. And Western blotting analysis was used to examine the expression of protein of GRP78, SREBP-1c and LXRs. Results Western blotting analysis showed that GRP78 protein expression in the experimental group was remarkably higher than that inthe control group (P<0. 05), indicating the successful establishment of the endoplasmic reticulum stress model in hepatocytes. The hepatocyte fatty deposition in the experimental group was significantly more than that in the control group 48 h after thapsigargin exposure(P<0. 01). The expression of SREBP-1c mRNA and protein in the experimental group was significantly higher than that in the control group (P<0. 05), and the expression of LXRs mRNA and proteinwas not significantly between the two groups. Conclusion Endoplasmic reticulum stress may induce hepatocyte fatty deposition throuth up-regulating SREBP-1c, and LXRs is not involved in the process.
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Objective To observe the fatty deposition in thapsigargin-induced endoplasmic reticulum stress model in hepatocytes and to discuss the possible mechanism. Methods Hepatocytes (L02 cell and HepG2 cell line) were divided into control group and experimental group (treated with 1 μmol/L thapsigargin). Fatty deposition in the hepatocytes was observed by biochemical assay and oil red O staining. Real-time PCR was used to test the expression of SREBP-1c and LXRs mRNA. And Western blotting analysis was used to examine the expression of protein of GRP78, SREBP-1c and LXRs. Results Western blotting analysis showed that GRP78 protein expression in the experimental group was remarkably higher than that inthe control group (P<0. 05), indicating the successful establishment of the endoplasmic reticulum stress model in hepatocytes. The hepatocyte fatty deposition in the experimental group was significantly more than that in the control group 48 h after thapsigargin exposure(P<0. 01). The expression of SREBP-1c mRNA and protein in the experimental group was significantly higher than that in the control group (P<0. 05), and the expression of LXRs mRNA and proteinwas not significantly between the two groups. Conclusion Endoplasmic reticulum stress may induce hepatocyte fatty deposition throuth up-regulating SREBP-1c, and LXRs is not involved in the process.
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Background Liver X receptors (LXRs) are members of the nuclear hormone receptor superfamily which involve in energy metabolism of intracellular cholesterol and glucose regulation.Objective To investigate the effect of Liver X receptors (LXRs) agonists on the hypertrophy induced by angiotensin Ⅱ(Ang Ⅱ) in the murine HL-1 cardiomyocytes in vitro.Methods Hypertrophy in murine HL-1 cardiomyocytes was induced by Ang Ⅱ and treated with LXRs agonist T0901317 (1 ?mol/L).Immunofluorescent staining was carried out to identify the HL-1 cells.The surface area of HL-1 cells was analyzed by using NIH Image J software.The synthetic rate of protein in HL-1 cells was detected by {}3H leucine incorporation.The mRNA level of atrial natriuretic peptide (ANP) was measured by quantitative realtime PCR.Results HL-1 cells hypertrophy induced by Ang Ⅱ were manifested by the increases in surface area,mRNA expression of ANP,and {}3H leucine incorporation(control group vs Ang Ⅱ group:cell surface:1.00?0.16 vs 2.00?0.21,ANP mRNA:1.00?0.02 vs 1.58?0.27,{}3H leucine incorporation:1.00?0.03 vs 1.44?0.07,respectively,all P
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Objective To study the protective mechanism of S-adenosylmethionine ( SAM) underlying liver injury induced by lipopolysaccharides ( LPS). Methods One hundred BABL/c mice were randomly divided into LPS group and SAM group. Mice in LPS group were intraperitoneally injected with 10 mg/kg LPS,and the mice in SAM group were injected with 100 mg/kg SAM 2 h before receiving the same dose of LPS. The survival rate of mice in 2 groups was recorded in 24,48,72 and 120 h after LPS injection. Histopathological changes in liver of mice were examined in 0,1,3,6,12 and 24 h after LPS injection. Tumor necrosis factor-? ( TNF-?) and interleukin-10 ( IL-10) levels in serum were measured by ELISA analysis at above time points. Expression of Toll-like receptor 4 ( TLR4) and liver X receptor ? ( LXR?) in hepatic tissues was detected by immunohistochemistry and Western blotting. Results SAM increased the survival rate of mice from 50. 0% ,40. 0% ,30. 0% ,and 30. 0% before LPS injection to 80. 0% ,70. 0% ,60. 0% ,and 50. 0% after its injection ( P