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Table 1.

Fatty acid composition of cocoa butter and refined and virgin pumpkin seed oil.

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Table 2.

Phytochemical content of cocoa butter and refined and virgin pumpkin seed oil

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Fig 1.

Refined and virgin pumpkin seed oils have beneficial effects on plasma lipids in cholesterol-fed ApoE*3Leiden mice.

Mice were fed a Western type diet (CON) containing cocoa butter (15% w/w of diet) for 20 weeks. The cocoa butter was in part replaced by refined pumpkin seed oil (REF) or virgin pumpkin seed oil (VIR) (each 9% w/w of diet). A: Plasma cholesterol levels over the course of the study, showing lower levels in REF and VIR-fed animals. B: Area under the curve analysis (AUC, expressed in arbitrary units; AU) of plasma cholesterol levels (t = 0 until t = 20 weeks) shows additional cholesterol-lowering effect of VIR compared with REF. C: Lipoprotein profile for cholesterol distribution in VLDL, LDL and HDL-sized particles shows cholesterol-lowering effect mainly confined to VLDL-sized particles. D: Plasma triglycerides over the course of the study were lowered by both REF and VIR. E: Area under the curve analysis of plasma triglyceride levels (t = 0 until t = 20 weeks) shows a reduction by VIR and REF. Data are mean±SEM. * p≤0.05, ** p≤0.01, *** p≤0.001 compared with CON. # p≤0.05, ## p≤0.01 for VIR compared with REF.

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Fig 2.

Virgin pumpkin seed oil reduces circulating markers of inflammation in cholesterol-fed ApoE*3Leiden mice.

Mice were fed a Western type control diet (CON) or CON diet containing 9% refined pumpkin seed oil (REF) or 9% virgin pumpkin seed oil (VIR) for 20 weeks. A: Plasma SAA levels were reduced by VIR. Liver damage marker B: ASAT and C: ALAT were reduced by VIR but not by REF. D: Plasma sVCAM-1 levels in VIR animals were lower throughout the duration of the study. Data are mean±SEM. * p≤0.05, ** p≤0.01 compared with CON. # p≤0.05 for VIR compared with REF.

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Fig 3.

Virgin pumpkin seed oil attenuates development of NAFLD in cholesterol-fed ApoE*3Leiden mice.

Mice were fed a Western type control diet (CON) or CON diet containing 9% refined pumpkin seed oil (REF) or 9% virgin pumpkin seed oil (VIR) for 20 weeks. A: Liver weight (expressed as percentage of terminal body weight) was reduced by REF and VIR. B: representative photomicrographs of HE-stained liver sections show presence of micro- (grey arrows) and macro- (white arrows)vesicular steatosis and inflammatory cell clusters (black arrows) in CON-fed animals, which was less pronounced in REF and more strongly reduced in VIR. C: Histological quantitative scoring of macrovesicular steatosis showed significant reduction in VIR. D: Hepatic triglyceride levels (biochemically determined) were reduced in both REF and VIR while only VIR significantly reduced E: hepatic cholesteryl ester content and F: free (unesterified) cholesterol levels. G: Histological quantification of number of inflammatory cell aggregates revealed a significant attenuation of hepatic inflammation by VIR. Data are mean±SEM. * p≤0.05, ** p≤0.01, *** p≤0.001 compared with CON. # p≤0.05, ### p≤0.001 for VIR compared with REF.

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Fig 4.

Atherosclerosis development is reduced with virgin pumpkin seed oil.

Mice were fed a Western type control diet (CON) or CON diet containing 9% refined pumpkin seed oil (REF) or 9% virgin pumpkin seed oil (VIR) for 20 weeks. A: representative photomicrographs of HPS-stained cross sections of the aortic root show pronounced development of atherosclerosis in CON animals, which was less pronounced in REF and strongly reduced by VIR. B: Morphometric analysis of lesion area revealed a significant decrease in atherosclerotic lesion area by REF and VIR. C: Anti-atherogenic effects of pumpkin seed oils are specific on severe lesion types. D: Average lesion size was reduced in REF and VIR. E: Immunohistochemical staining for MAC-3 (CD107b) followed by quantification of positively stained area showed that both REF and VIR reduced the macrophage content of type V lesions. Data are mean±SEM. * p≤0.05, ** p≤0.01 compared with CON.

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Fig 5.

Refined and virgin pumpkin seed oils modulate lipid metabolism and inflammatory gene expression.

Mice were fed a Western type control diet (CON) or CON diet containing 9% refined pumpkin seed oil (REF) or 9% virgin pumpkin seed oil (VIR) for 20 weeks. A: Hepatic lipogenic gene expression (Srebf1, Fasn, Dgat1) was reduced in both REF and VIR. B: Hepatic expression of genes involved in fatty acid catabolism (Ppara, Cpt1a, Acox1) was upregulated in VIR and to a lesser extent in REF. C. Only VIR reduced hepatic expression of inflammatory genes (Ccl2, Tnf, IL1b). All gene expression data are expressed as fold-change relative to CON. Data are mean±SEM. * p≤0.05, ** p≤0.01, *** p≤0.001 compared with CON, # p≤0.05, ### p≤0.001 for VIR compared with REF.

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