The cis-9,trans-11 isomer of conjugated linoleic acid (CLA) lowers plasma triglyceride and raises HDL cholesterol concentrations but does not suppress aortic atherosclerosis in diabetic apoE-deficient mice

OBJECTIVE: Reduction in atherosclerosis has been reported in experimental animals fed mixtures of conjugated linoleic acid (CLA). In this study, the major naturally occurring CLA isomer (cis-9,trans-11) was tested in an atherosclerosis-prone mouse model. METHODS: In a model of insulin deficient apoE deficient mice, 16 animals were fed for 20 weeks with supplemental CLA (09.%, w/w) and compared with a similar number of mice of this phenotype. A control comparison was made of metabolic changes in non-diabetic apoE deficient mice that develop little atherosclerosis over 20 weeks. At 20 weeks, plasma lipids were measured and aortic atherosclerosis quantified by Sudan staining in the arch, thoracic and abdominal segments. RESULTS: The diabetic apoE deficient mice developed marked dyslipidemia, primarily as cholesterol-enriched chylomicron and VLDL-sized lipoproteins and atherosclerosis in the aortic arch. However, there were no significant differences between CLA fed and non-CLA fed mice in either phenotype in plasma cholesterol concentration (in diabetic: 29.4+/-7.7 and 29.5+/-5.9 mmol/L, respectively) or in the area of aortic arch atherosclerosis (in diabetic: 24.8+/-10.3 and 27.6+/-7.7%, respectively). However, among diabetic mice the triglyceride concentration in triglyceride-rich lipoproteins was significantly lower in those fed CLA (for plasma 2.2+/-0.8 to 1.1+/-0.3 mmol/L; P<0.001), a significant difference that was seen also in the non-diabetic mice in which HDL cholesterol increased significantly with CLA (0.35+/-0.12-0.56+/-0.15 mmol/L). CONCLUSION: In this atherosclerosis-prone model, the diabetic apoE deficient mouse, supplemental 0.9% CLA (cis-9,trans-11) failed to reduce the severity of aortic atherosclerosis, although plasma triglyceride concentration was substantially lowered and HDL cholesterol raised.     

Effect of cis—9,trans—11—conjugated linoleic acid on cell cycle of gastric adenocarcinoma cell line（SGC—7901）

AIM: To determine the effect of cis -9, trans -11-conjugated linoleic acid (c9, t11-CLA) on the cell cycle of gastric cancer cells (SGC-7901) and its possible mechanism in inhibition cancer growth. METHODS: Using cell culture and immunocytochemical techniques, we examined the cell growth, DNA synthesis, expression of PCNA, cyclin A, B(1), D(1), p16(ink4a) and p21(cip/waf1) of SGC-7901 cells which were treated with various c9, t11-CLA concentrations (25, 50, 100 and 200 micromol.L(-1))of c 9, t 11-CLA for 24 and 48h, with a negative control (0.1% ethane). RESULTS: The cell growth and DNA synthesis of SGC-7901 cells were inhibited by c9, t11-CLA.SGC-7901 cells. Eight day after treatment with various concentrations of c9, t11-CLA mentioned above, the inhibition rates were 5.92%, 20.15%, 75.61% and 82.44%, respectively and inhibitory effect of c9, t11-CLA on DNA synthesis (except for 25 micromol.L, 24h) showed significantly less (3)H-TdR incorporation than that in the negative controls (P<0.05 and P<0.01). Immunocytochemical staining demonstrated that SGC-7901 cells preincubated in media supplemented with different c9, t11-CLA concentrations at various times significantly decreased the expressions of PCNA (the expression rates were 7.2-3.0%, 24h and 9.1-0.9% at 48h, respectively), Cyclin A (11.0-2.3%, 24h and 8.5-0.5%,48h), B(1) (4.8-1.8% at 24h and 5.5-0.6% at 48h)and D(1) (3.6-1.4% at 24h and 3.7%-0 at 48h) as compared with those in the negative controls(the expressions of PCNA, Cyclin A, B(1) and D(1) were 6.5% at 24h and 9.0% at 48h, 4.2% at 24h and 5.1% at 48h, 9.5% at 24h and 6.0% at 48h,respectively)(P<0.01), whereas the expressions of P16(ink4a) and P21(cip/waf1), cyclin-dependent kinases inhibitors(CDKI), were increased. CONCLUSION: The cell growth and proliferation of SGC-7901 cell is inhibited by c9, t11-CLA via blocking the cell cycle, with reduced expressions of cyclin A,B(1) and D(1) and enhanced expressions of CDKI(P16(ink4a) and p21(cip/waf1)).     

Effect of apoptosis on gastric adenocarcinoma cell line SGC—7901 induced by cis—9,trans—11—conjugated linoleic acid

AIM: To determine the effect of apoptosis on gastric cancer cells (SGC-7901) induced by cis-9, trans-11-conjugated linoleic acid (c9, t11-CLA) and its possible mechanism in the inhibition of cancer cells growth. METHODS: Using cell culture, flow cytometery and immunocytochemical techniques, we examined the cell growth, frequency of apoptosis and distribution of cell cycle, expression of ki67, bcl-2, Fas, and c-myc of SGC-7901 cells which were treated with various c9, t11-CLA concentrations (25,50,100 and 200 micromol x L(-1)) of c9, t11-CLA for 24 h and 48 h, with a negative control (0.1 % ethanol). RESULTS: The growth of SGC-7901 cells was inhibited by c9,t11-CLA. Eight days after treatment with various concentrations of c9,t11-CLA, as mentioned above, the inhibition rates were 5.9 %, 20.2 %,75.6 % and 82.4 %, respectively. The frequency of apoptosis on SGC-7901 cells induced by different concentrations of c9, t11-CLA (except for 25 micromol.L(-1), 24 h) was significantly greater than that in the negative control (P<0.01). To further investigate the influence of the cell cycle progression, we found that apoptosis induced by c9, t11-CLA may be involved in blocking the cell cycle of SGC-7901 cells. Immunocytochemical staining demonstrated that SGC-7901 cells preincubated in media supplemented with different c9, t11-CLA concentrations for various time periods significantly decreased the expressions of ki67 (the expression rates were 18.70-3.20 %, at 24 h and 8.10-0.20 % at 48 h, respectively), bcl-2 (4.30-0.15 % at 24 h and 8.05 %-0 at 48 h), and c-myc (4.85-2.20 % at 24 h and 4.75-0.30 % at 48 h) as compared with those in the controls (the expressions of ki67, bcl-2, and c-myc were 15.1 % at 24 h and 13.5 % at 48 h, 6.80 % at 24 h and 8.00 % at 48 h, 5.50 % at 24 h and 5.30 % at 48 h, respectively) (P<0.01), whereas the expressions of Fas were increased (0.60-2.75 %, 24 h and 0.45-5.95 %, 48 h). CONCLUSION: The growth and proliferation of SGC-7901 cells are inhibited by c9, t11-CLA via blocking the cell cycle, pathways of bcl-2-associated mitochondria with reduced expression of bcl-2 and Fas-associated death domain protein (FADD) with enhanced expression of Fas. But expression of c-myc on SGC-7901 cells is lower than that in negative control, which needs to be studied further.     

Effects of a dairy product (pecorino cheese) naturally rich in cis-9, trans-11 conjugated linoleic acid on lipid,inflammatory and haemorheological variables: A dietary intervention study

Background and aimSome studies recently reported a favourable effect for cis-9, trans-11 conjugated linoleic acid (CLA) on plasma lipoprotein profile of healthy subjects. Aim of this crossover intervention study was to evaluate the influence of a short-term dietary intake of a cheese derived from sheep's milk naturally rich in CLA on several atherosclerotic biomarkers, in comparison with a commercially available cheese.Methods and resultsTen subjects (6 F; 4 M) with a median age of 51.5 followed for 10 weeks a diet containing 200 g/week of cheese naturally rich in CLA (intervention period) and for the same period a diet containing a commercially available cheese of the same quantity (placebo period). Consumption of the dairy product naturally rich in cis-9, trans-11 CLA determined a significant (p < 0.05) reduction in inflammatory parameters such as interleukin-6 (pre: 8.08 ± 1.57 vs. post: 4.58 ± 0.94 pg/mL), interleukin-8 (pre: 45.02 ± 5.82 vs. post: 28.59 ± 2.64 pg/mL), and tumour necrosis factor-α (pre: 53.58 ± 25.67 vs. post: 32.09 ± 17.42 pg/mL) whereas no significant differences in the placebo period were observed. With regard to haemorheological parameters, the test period significantly ameliorated erythrocytes' filtration rate (pre: 7.61 ± 0.71% vs. post: 9.12 ± 0.97%; p = 0.03) with respect to the placebo period. Moreover, a reduction in the extent of platelet aggregation, induced by arachidonic acid [pre: 87.8 ± 1.76% vs. post: 77.7 ± 3.56%; p = 0.04] was observed during the test period in comparison with the placebo period.ConclusionsDietary short-term intake of the tested dairy product naturally rich in cis-9, trans-11 CLA appeared to cause favourable biochemical changes of atherosclerotic markers.     

Simvastatin but not bezafibrate decreases plasma lipoprotein-associated phospholipase A(2) mass in type 2 diabetes mellitus: Relevance of high sensitive C-reactive protein, lipoprotein profile and low-density lipoprotein (LDL) electronegativity

ObjectivePlasma lipoprotein-associated phospholipase A₂ (Lp-PLA₂) levels predict incident cardiovascular disease, impacting Lp-PLA₂ as an emerging therapeutic target. We determined Lp-PLA₂ responses to statin and fibrate administration in type 2 diabetes mellitus, and assessed relationships of changes in Lp-PLA₂ with subclinical inflammation and lipoprotein characteristics.MethodsA placebo-controlled cross-over study (three 8-week treatment periods with simvastatin (40 mg daily), bezafibrate (400 mg daily) and their combination) was carried out in 14 male type 2 diabetic patients. Plasma Lp-PLA₂ mass was measured by turbidimetric immunoassay.ResultsPlasma Lp-PLA₂ decreased (? 21 ± 4%) in response to simvastatin (p < 0.05 from baseline and placebo), but was unaffected by bezafibrate (1 ± 5%). The drop in Lp-PLA₂ during combined treatment (? 17 ± 3%, p < 0.05) was similar compared to that during simvastatin alone. The Lp-PLA₂ changes during the 3 active lipid lowering treatment periods were related positively to baseline levels of high sensitive C-reactive protein, non-HDL cholesterol, triglycerides, the total cholesterol/HDL cholesterol ratio and less LDL electronegativity (p < 0.02 to p < 0.01), and inversely to baseline Lp-PLA₂ (p < 0.01). LpPLA₂ responses correlated inversely with changes in non-HDL cholesterol, triglycerides and the total cholesterol/HDL cholesterol ratio during treatment (p < 0.05 to p < 0.02).ConclusionsIn type 2 diabetes mellitus, plasma Lp-PLA₂ is likely to be lowered by statin treatment only. Enhanced subclinical inflammation and more severe dyslipidemia may predict diminished LpPLA₂ responses during lipid lowering treatment, which in turn appear to be quantitatively dissociated from decreases in apolipoprotein B lipoproteins. Conventional lipid lowering treatment may be insufficient for optimal LpPLA₂ lowering in diabetes mellitus.