ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of niacin on HDL-induced cholesterol efflux and LXRalpha expression in adipocytes from hypercholesterolemic rabbits.</p><p><b>METHODS</b>Twelve rabbits fed with high-cholesterol diet for 8 weeks were randomly divided into two groups: (1) high cholesterol group (n = 6): maintained high cholesterol diet for 6 weeks; (2) niacin group (n = 6): the same cholesterol diet plus niacin (0.2 g . kg(-1). d(-1)) for 6 weeks. Control group (n = 6) was fed with normal diet for 14 weeks. Subcutaneous adipose was collected for adipocyte culture. RT-PCR was used to evaluate adipocytes LXRalpha mRNA expressions. Cholesterol efflux rate was determined through measuring release of radioactivity from 3H-cholesterol prelabeled cells into medium containing HDL. The direct effect of niacin on LXRalpha and PPARgamma mRNA expression in primary rabbit adipocytes was assayed.</p><p><b>RESULTS</b>High cholesterol diet resulted in decreased LXRalpha mRNA expressions and reduced cholesterol efflux rate in adipocytes. Six weeks of niacin treatment significantly enhanced the cholesterol efflux from adipocytes, which was related to the increased mRNA expressions of LXRalpha (r = 0.71, P < 0.05). In vitro study, niacin dose-dependently stimulated LXRalpha and PPARgamma mRNA expression in cultured adipocytes and there were positive correlations between various doses of niacin-induced cholesterol efflux and LXRalpha and PPARgamma mRNA expression (r = 0.83 P < 0.01, r = 0.76 P < 0.05, respectively).</p><p><b>CONCLUSION</b>LXRalpha and PPARgamma might play an important role in cholesterol efflux from adipocytes. Niacin can up-regulate LXRalpha and PPARgamma mRNA expressions and promote the cholesterol efflux in adipocytes from hypercholesterolemic rabbits.</p>
Subject(s)
Animals , Male , Rabbits , Adipocytes , Metabolism , Cholesterol , Metabolism , DNA-Binding Proteins , Metabolism , Disease Models, Animal , Hypercholesterolemia , Drug Therapy , Metabolism , Hyperlipidemias , Drug Therapy , Metabolism , Liver X Receptors , Niacin , Pharmacology , Therapeutic Uses , Orphan Nuclear Receptors , PPAR gamma , Metabolism , Receptors, Cytoplasmic and Nuclear , MetabolismABSTRACT
OBJECTIVE@#To explore the effect of niacin on the serum adiponectin concentration in hypercholesterolemia rabbit and the adiponectin concentration secreted by adipocytes in normal rabbits.@*METHODS@#Ten male New Zealand white rabbits fed with high cholesterol diet for 8 weeks were randomly divided into 2 groups: (1) The high cholesterol group maintained a high cholesterol diet for 8 weeks. (2) The same cholesterol diet plus niacin (0.4g/kg*d ) were administrated for 6 weeks in the niacin group. A control group was fed with normal diet for 14 weeks. Subcutaneous adipose from the control group was collected for adipocyte culture. Matured adipocytes were incubated with various concentrations of niacin (0, 0.25, 0.5, 1.0, and 2.0micromol/L). Adiponectin concentrations in the serum and adipocyte culture supernatant were measured by enzyme-linked-immunosorbent assay.@*RESULTS@#Compared with the control group, rabbits in the high cholesterol group showed higher serum levels of total cholesterol, and low density lipoprotein cholesterol (LDL-C), all of which were significantly reduced by niacin treatment (P<0.01),and serum high density lipoprotein-cholesterol (HDL-C) significantly increased (P<0.01). At 8th week, the mean adiponectin concentration of rabbits fed with high cholesterol diet was significantly lower than that of the control group[(1.268+/-0.039)mg/L vs.(1.449+/-0.107)mg/L,P<0.01]. Niacin treatment significantly elevated the serum adiponectin level which was positively related to HDL-C,and negatively related to TC and LDL-C. Cell experiment in vitro indicated that niacin could significantly induce the adiponectin secretion of adipocytes in a dose-dependent manner.@*CONCLUSION@#Niacin can significantly promote the adiponectin secretion of adipocytes, suggesting that niacin probably has an ability of elevating the serum adiponectin level in addition to lipid-lowering effect.
Subject(s)
Animals , Male , Rabbits , Adipocytes , Cell Biology , Metabolism , Adiponectin , Blood , Metabolism , Cholesterol , Blood , Cholesterol, Dietary , Toxicity , Cholesterol, HDL , Blood , Cholesterol, LDL , Blood , Dose-Response Relationship, Drug , Hypercholesterolemia , Blood , Hypolipidemic Agents , Pharmacology , Niacin , Pharmacology , Random AllocationABSTRACT
OBJECTIVE@#To explore whether oxidized low-density lipoprotein (ox-LDL) can stimulate the cholesterol efflux in fully differentiated 3T3-L1 cells and the possible mechanism.@*METHODS@#Fully differentiated 3T3-L1 cells were incubated in the medium containing various concentrations of ox-LDL ( 0 to 50 microg/mL) for 8 or 24 hours. 22(R)-Hydroxycholesterol (10 micromol/L) was exposed to preconditioned adipocytes with 25 microg/mL ox-LDL for 24 hours. Reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate ATP binding cassette transporter A1 (ABCA1), scavenger receptor class B type I (SR-BI), and liver X receptor alpha (LXRalpha) mRNA expression. Cholesterol efflux mediated by apolipoprotein A-I (apoA-I) was determined using liquid scintillator.@*RESULTS@#Low levels (12.5-25 microg/mL) of ox-LDL could increase cholesterol efflux via the enhancement of ABCA1 pathway and SR-BI expression, whereas the higher concentration (50 microg/mL) could not. In adipocytes preincubated with 25 microg/mL ox-LDL for 24 hours, 22(R)-hydroxycholesterol could increase ABCA1 and LXRalpha mRNA and apoA-I-mediated cholesterol efflux, but had no effect on the SR-BI mRNA expression.@*CONCLUSION@#Low levels of ox-LDL may enhance the LXRalpha-ABCA1-apoA-I pathway in adipocytes, up-regulate SR-BI mRNA expression, and then increase the cholesterol efflux. This new effect of ox-LDL will not only make contribution to cholesterol homeostasis in adipocytes, but also be potentially atheroprotective.