Omega 3 fatty acids promote macrophage reverse cholesterol transport in hamster fed high fat diet.

The aim of this study was to investigate macrophage reverse cholesterol transport (RCT) in hamster, a CETP-expressing species, fed omega 3 fatty acids (ω3PUFA) supplemented high fat diet (HFD). Three groups of hamsters (n = 6/group) were studied for 20 weeks: 1) control diet: Control, 2) HFD group: HF and 3) HFD group supplemented with ω3PUFA (EPA and DHA): HFω3. In vivo macrophage-to-feces RCT was assessed after an intraperitoneal injection of (3)H-cholesterol-labelled hamster primary macrophages. Compared to Control, HF presented significant (p<0.05) increase in body weight, plasma TG (p<0.01) and cholesterol (p<0.001) with an increase in VLDL TG and in VLDL and LDL cholesterol (p<0.001). Compared to HF, HFω3 presented significant decrease in body weight. HFω3 showed less plasma TG (p<0.001) and cholesterol (p<0.001) related to a decrease in VLDL TG and HDL cholesterol respectively and higher LCAT activity (p<0.05) compared to HF. HFω3 showed a higher fecal bile acid excretion (p<0.05) compared to Control and HF groups and higher fecal cholesterol excretion (p<0.05) compared to HF. This increase was related to higher gene expression of ABCG5, ABCA1 and SR-B1 in HFω3 compared to Control and HF groups (<0.05) and in ABCG1 and CYP7A1 compared to HF group (p<0.05). A higher plasma efflux capacity was also measured in HFω3 using (3)H- cholesterol labeled Fu5AH cells. In conclusion, EPA and DHA supplementation improved macrophage to feces reverse cholesterol transport in hamster fed HFD. This change was related to the higher cholesterol and fecal bile acids excretion and to the activation of major genes involved in RCT

n-3 PUFA prevent metabolic disturbances associated with obesity and improve endothelial function in golden Syrian hamsters fed with a high-fat diet

International audienceGlucose intolerance and dyslipidaemia are independent risk factors for endothelium dysfunction and CVD. The aim of the present study was to analyse the preventive effect of n-3 PUFA (EPA and DHA) on lipid and carbohydrate disturbances and endothelial dysfunction. Three groups of adult hamsters were studied for 20 weeks: (1) control diet (Control); (2) high-fat diet (HF); (3) high-fat diet enriched with n-3 PUFA (HFn-3) groups. The increase in body weight and fat mass in the HF compared to the Control group (P<0.05) was not found in the HFn-3 group. Muscle TAG content was similar in the Control and HF groups, but significantly lower in the HFn-3 group (P=0.008). Glucose tolerance was impaired in the HF compared to the Control group, but this impairment was prevented by n-3 PUFA in the HFn-3 group (P<0.001). Plasma TAG and cholesterol were higher in the HF group compared to the Control group (P<0.001), but lower in the HFn-3 group compared to the HF group (P<0.001). HDL-cholesterol was lower in the HFn-3 group compared to the Control and HF groups (P<0.0005). Hepatic secretion of TAG was lower in the HFn-3 group compared to the HF group (P<0.005), but did not differ from the Control group. Hepatic gene expression of sterol regulatory element-binding protein-1c, diacylglycerol O-acyltransferase 2 and stearyl CoA desaturase 1 was lower in the HFn-3 group, whereas carnitine palmitoyl transferase 1 and scavenger receptor class B type 1 expression was higher (P<0.05). In adipocytes and adipose macrophages, PPAR gamma and TNF alpha expression was higher in the HF and HFn-3 groups compared to the Control group. Endothelium relaxation was higher in the HFn-3 (P<0.001) than in the HF and Control groups, and was correlated with glucose intolerance (P=0.03) and cholesterol (P=0.0003). In conclusion, n-3 PUFA prevent some metabolic disturbances induced by high-fat diet and improve endothelial function in hamsters

Effect of the three diets on reverse cholesterol transport.

<p><b>A</b>: ³H-tracer appearance in plasma at time 24, 48 and 72 hours after injection. <b>B</b>: Liver ³H-tracer recovery at 72 h after injection of labeled and acetylated LDL-loaded macrophages. <b>C</b>: ³H-tracer recovery in fecal cholesterol and bile acids. Data are expressed as percent cpm injected and mean ± SEM (n = 6 per group; * p<0.05 different from Control; † p<0.05 different from HF.</p

Western blot analysis of hepatic SR-B1 protein in hamster fed control, HF or HF diet supplemented with omega 3 fatty acids.

<p>Values are means ± SEM; n = 2 for Control group; n = 3 for HF and HFω3 groups.</p

[³H]-cholesterol efflux from Fu5AH.

<p>[³H]-cholesterol labeled Fu5AH cells were incubated with hamster serum and efflux was performed for 4 h. Data are mean ± SEM. n = 6 per group.</p

Representative TG (A) and cholesterol (B) profiles of Control, HF and HFω3 groups performed by FPLC.

<p>Representative TG (A) and cholesterol (B) profiles of Control, HF and HFω3 groups performed by FPLC.</p

Effect of different diets on body weight, plasma lipid parameters and CETP and LCAT activities.

<p>Values are mean ± SEM, n = 6 per group.</p>*<p>different from Control (*p<0.05 ** p<0.01; ***p<0.001).</p>†<p>different from HF († p<0.05, †† p<0.01; ††† p<0.001).</p

Effect of the three diets on hepatic gene expression.

<p>Relative gene expression in liver in Control, HF and HFω3 groups. Values are means ± SEM (n = 6 per group; * p<0.05 different from Control; † p<0.05 different from HF). (ABCA1, ATP binding cassette protein A1, CYP7A1, Cytochrome P450 family 7 subfamily A polypeptide 1, SR-B1, scavenger receptor class B type 1, and LDLr low density lipoprotein receptor).</p

Apple Supplementation Improves Hemodynamic Parameter and Attenuates Atherosclerosis in High-Fat Diet-Fed Apolipoprotein E-Knockout Mice

International audienceEpidemiological studies describe the association between apple consumption and improved cardiovascular and metabolic dysfunction. Our recent multiparametric screening on cellular model studies has shown that apples exhibit vascular tropism including Granny Smith (GS) variety independently of the storage condition. The present study aimed to evaluate the cardiovascular and metabolic protection of supplementation of GS variety after storage in classic cold (GSCC) and extreme ultra-low oxygen conditions (GSXO) in the apolipoprotein E-deficient 8-week-old mice fed with high fat diet for 14 weeks. Supplementation with GSCC and GXO decreases circulating triglycerides, the expression of genes involved in lipogenesis, without change in cholesterol and glucose concentrations and HOMA-IR. Only GSXO supplementation ameliorates body weight gain, insulin level, and HDL/LDL ratio. GSXO supplementation does not modify cardiac parameters; while supplementation with GSCC decreases heart rate and improves cardiac output. Interestingly, GSCC and GSXO reduce systolic and diastolic blood pressure with a differential time course of action. These effects are associated with substantial decrease of atherosclerotic lesions. These data reinforce the knowledge about the vascular tropism of apple supplementation and underscore their ability to improve both cardiovascular and metabolic alterations in a mouse model of atherosclerosis