AIM:To study the role of c-Jun NH2-terminal kinase (JNK) in the development of insulin resistance induced by tumor necrosis factor-? (TNF-?) or H2O2 in 3T3-L1 adipocytes. METHODS:Differentiated 3T3-L1 adipocytes were pretreated with JNK1 small interfering RNA (siRNA) or JNK inhibitor SP600125,then exposed to 1 nmol/L of TNF-? or micromolar H2O2 generated by adding glucose oxidase (50 U/L) to the medium for 12 h. The cellular glucose uptake was determined by radioactive method. RESULTS:Compared to control adipocytes,12 h incubation with TNF-? or H2O2 led to 50%-55% reduction (P

AIM: To investigate the relationship between adiponectin gene SNP+45 polymorphism and coronary heart disease(CHD) in south China Han population.METHODS: The nondiabetic CHD patients diagnosed by the coronary angiography were selected as CHD subjects(153 cases),and 73 healthy adults served as normal control subjects.The polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) was performed to identify the distribution pattern of adiponectin gene SNP+45 in all subjects.The levels of plasma adiponectin were measured by ELISA.RESULTS: The frequency of T/G + G/G genotype and G allele in CHD patients were significantly higher than those in control subjects(P

Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) is a type-Ⅱ membrane protein belonging to the C-type lectin family molecules, which acts as a cell surface endocytosis receptor for atherogenic oxidized LDL (Ox-LDL). LOX-1 supports the binding internalization and proteolytic degradation of oxidized LDL, but not of significant amounts of acetylated LDL. LOX-1 is initially synthesized as a 40 kD precursor protein with N-linked high mannose-type carbohydrate, which is further glycosylated and processed into a 48-kD mature form. In vivo, endothelial cells that cover early therosclerotic lesions, intimal macrophages and smooth muscle cells in advanced atherosclerotic plaques express LOX-1. LOX-1 is cleaved at membrane proximal extracellular domain and released from the cell surface. Measurement of soluble LOX-1 in vivo may provide novel diagnostic strategy for the evaluation and prediction of atherosclerosis and vascular diseases.

AIM: To study the role of c-Jun NH_2-terminal kinase (JNK) in the development of insulin resistance induced by tumor necrosis factor-α (TNF-α) or H_2O_2 in 3T3-L1 adipocytes. METHODS: Differentiated 3T3-L1 adipocytes were pretreated with JNK1 small interfering RNA (siRNA) or JNK inhibitor SP600125, then exposed to 1 nmol/L of TNF-α or micromolar H_2O_2 generated by adding glucose oxidase (50 U/L) to the medium for 12 h. The cellular glucose uptake was determined by radioactive method. RESULTS: Compared to control adipocytes, 12 h incubation with TNF-α or H_2O_2 led to 50%-55% reduction (P<0.01) of the insulin-dependent glucose uptake. JNK1 siRNA transfection significantly inhibited JNK1 expression and blocked the TNF-α or H_2O_2-induced impairments of cellular glucose uptake. Pretreatment with SP600125 (20 μmol/L) resulted in significant increases in insulin-stimulated glucose uptakes in both TNF-α (66%) and H_2O_2 (62%) treated adipocytes (P<0.01). CONCLUSION: JNK plays a key role in TNF-α or H_2O_2 induced insulin resistance in 3T3-L1 adipocytes, and inhibition of JNK over-activation may be a new therapeutic target for insulin resistance.

Objective To explore the molecular basis of vascular endothelial cell's injury by cellular S-adenosylhomocysteine (SAH) accumulation, and the mechanism for cardiovascular disease induced by dietary high methionine intake. Method After human umbilical vein endothelial cells (HUVEC) were treated without (normal) or with different concentrations of potent S-adenosylhomocysteine hydrolase (SAHH) inhibitor 3-deazaadenosine (DZA) for 24, 48 or 72h, the level of intracellular inflammatory monocyte chemoattractant protein-1 (MCP-1) was measured with enzyme linked immunosorbent assay (ELISA). Then, the relative expression of MCP-1 mRNA was detected with quantitative reverse transcription polymerase chain reaction (qRT-PCR). Furtheremore, the methylated state of MCP-1 gene promoter was analyzed with methylation special PCR (MSP) method. Results The level of intracellular MCP-1 was increased in HUVEC incubated with DZA than normal (P

AIM: To explore the effects of oxidized low density lipoprotein (OxLDL) and one of its component— lysophosphatidylcholine (LPC) on cholesterol efflux from mouse macrophage foam cells. METHODS: (1) Cholesterol efflux induced by apoAI from mouse peritoneal macrophage foam cells loaded with OxLDL or acylated LDL(AcLDL) was measured. (2) Cholesterol efflux induced by LPC and apoAI from macrophage foam cells separated from normal or apoE gene deficient (E 0) mouse loaded with AcLDL were measured. RESULTS: (1) When the macrophage foam cells were incubated with apoAI, cholesterol efflux from AcLDL-induced macrophage foam cells increased significantly compared to that of OxLDL-induced macrophage foam cells. (2) LPC promoted cholesterol efflux from macrophage foam cells in relation to both dosage and time. When LPC was incubated with E 0 mouse macrophage foam cells, the released cholesterol mass was significantly lower than that of normal mouse macrophage foam cells. It was also found that cholesterol efflux induced by apoAI normally occurred in E 0 mouse macrophage foam cells. CONCLUSIONS: (1) OxLDL accumulated cholesterol in macrophages and impair cholesterol efflux. (2) LPC induced cholesterol efflux from macrophage foam cells, which may occur via apoE pathway.

AIM: To observe the relationship between UCP2 mRNA expression in white adipose tissue and diet-induced obesity in SR-A I/II gene knock-out(SR-AⅠ/Ⅱ-/-) mice.METHODS: Fluorescent quantitative RT-PCR was used to detect UCP2 mRNA expression in mice epididymal white adipose tissue.The cellular morphological changes were analyzed by using image analysis.Serum TG,TC and LDL-C concentrations were measured by enzymatic determination.RESULTS: After fed with high fat diet for 12 weeks,average body weight of SR-A I/II-/-mice was much higher than that of wild type(SR-A I/II+/+) control mice(P

Objective To compare the characteristics of food and nutrition intake in type 2 diabetes mellitus (T2DM) patients with or without carotid atherosclerosis and analyze the relationship between diets/C-reactive protein (CRP) and carotid intima-media thickness (C-IMT). Methods Sixty patients with T2DM were enrolled and divided into two groups based on C-IMT: group A (C-IMT ＜ 1 mm, n=30) and group B (C-IMT≥1 mm, n=30). All subjects were investigated with questionnaires including 3-day food recall They all took somatometric measurement. Blood and urine samples were collected in all subjects to examine the levels of high sensitive-CRP,C-peptide, blood glucose, glycosylated hemoglobin, blood lipid, renal function, urine microalbumin, and other indicators. Results The intakes of vegetables, fruits, and aquatic products were significantly higher in group A than in group B ( P ＜ 0. 05 ). The intake of vitamin C in group A was significantly higher than that in group B ( P ＜0. 05 ). The levels of CRP in group B was significant higher than that in group A (P = 0. 000). Positive correlation was found between CRP level and C-IMT in T2DM patients ( r = 0. 36, P = 0. 004). Furthermore, CRP was negatively correlated with the intakes of vegetables and fruits ( r = - 0. 334, P = 0. 01 ), aquatic products ( r = -0. 315, P = 0. 016), and vitamin C ( r = - 0. 2786, P = 0. 038 ), respectively. The intake of fruits was negatively correlated with C-IMT (r, = -0. 33, P = 0. 01 ). Conclusions T2DM patients without carotid atherosclerosis intake more vegetables, fruits, aquatic products and vitamin C than those with atherosclerosis. Vegetables, fruits,sea foods and vitamin C may be the protective factors against atherosclerosis in T2DM patients. CRP is associated with the development of atherosclerosis in T2DM patients.

Objective To observe the alteration of scavenger receptor class A types Ⅰand Ⅱ (SR-AⅠ/Ⅱ) gene knock-out on lipid metabolism in mice fed with high-fat diet, and explore the underlying mechanism. Method The SR-AⅠ/Ⅱgene knock-out and wild-type male mice were fed with normal and high-fat diet for 12 w. Thereafter, the level of lipid metabolism (such as the levels of lipids in blood and liver) was detected with enzyme method or oil red O staining, and the expression of scavenger receptor class B typeⅠ(SR-BⅠ) and CD36 in liver was analyzed by RT-PCR. Results Under high-fat diet condition, as compared with wild-type mice, the levels of TG, TC, LDL and HDL in SR-AⅠ/Ⅱgene knock-out mice were decreased at 3, 6, 12 w (P0.05). Conclusion The alteration of lipid metabolism induced by high-fat diet in SR-AⅠ/Ⅱgene knock-out mice might be relative with the up-regulated SR-BⅠmRNA expression and the counter transport of peripheral lipids to liver.