New insights into the effects of onion consumption on lipid mediators using a diet-induced model of hypercholesterolemia

Abstract

The levels and roles of lipid mediators can be modified in response to nutritional stimuli. The aim of this study was to investigate shifts in oxylipin and sphingolipid profiles stimulated by a hypercholesterolemic (HC) diet along with the modulating effects of onion introduced as an antioxidant functional ingredient characterized in the diet (HCO). Oxylipin and sphingolipid profiles were determined in plasma and tissues from Wistar rats using LC-MS/MS. Plasma ω-3 and ω-6 PUFA-derived oxylipins decreased in rats after 7 weeks of HC feeding, but did not evidence a further shift with HCO diet. Onion ingredient supplementation modulated the hepatic concentrations of prostaglandins and enhanced ω-3 oxylipins in the liver of HCO-fed rats relative to the HC group. The HC diet induced shifts in plasma sphingolipids, increasing sphingoid bases, dihydroceramides and ceramides, whilst the sphingomyelin, hexosylceramide and lactosylceramide families decreased. The HCO diet modified some HC diet-induced changes in sphingolipids in liver and spleen tissue. Onion supplementation effected changes in lipid mediator levels in diet-induced hypercholesterolemic Wistar rats. The potential of onion as regulator of pro-inflammatory mediators, and possible enhancer of pro-resolution pathways, warrants further study of the interaction of functional ingredients with bioactive lipid mediators and their potential impact on inflammation, oxidative stress and organ dysfunction.

Keywords: Eicosanoids; Inflammation; Lipid profiling; Mass spectrometry; Oxylipins; Sphingolipids.

Graphical abstract

Fig. 1

Changes in oxylipins found in plasma and livers of Wistar rats after 7 weeks of experimental feeding. Control (C), high-cholesterol (HC) and high-cholesterol enriched with onion (HCO). Values greater and lower than 1 represent either an increase or a decrease relative to the control, respectively. n.d.: not determined. *Main enzymes/pathway responsible for oxylipin formation. In the absence of chiral determination, it is not possible to conclusively identify the synthetic source of the mono-hydroxy derivatives. Both potential enzymatic and non-enzymatic synthetic routes are indicated. AA: Arachidonic acid; LA: Linoleic acid; DHGLA: Dihomo-gamma-Linolenic acid; a-LA: alpha-Linolenic acid; EPA: Eicosapentaenoic acid; DHA: Docosahexaenoic acid; COX: Cyclooxygenase; LOX: Lipoxygenase; CYP450: Cytochrome P450; NE: Non-enzymatic oxidation; sEH: soluble epoxide hydrolase. An oxylipin nomenclature list is provided in Supplementary Table S3.

Fig. 2

Comparison of prostaglandins levels found in plasma and liver tissues from Wistar rats after 7 weeks of experimental feeding. Control (C), high-cholesterol (HC) and high-cholesterol enriched with onion (HCO). *P<0.05; **P<0.01; ***P<0.001; n.s.: not significant.

Fig. 3

Plasma sphingolipid pattern after 7 weeks of experimental feeding. Control (C), high-cholesterol (HC) and high-cholesterol enriched with onion (HCO). Red indicates an increase and blue a decrease in relative sphingolipid levels. C_16:0 species are shown as an example of changes produced in plasma by HC and HCO diets. *P<0.05; **P<0.01; ***P<0.001; n.s.: not significant. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article).

Fig. 4

Sphingolipid shifts produced in plasma and tissues after 7 weeks of experimental feeding. Control (C), high-cholesterol (HC) and high-cholesterol enriched with onion (HCO). Values greater and lower than 1 represent either an increase or a decrease relative to the control, respectively. n.d.: not determined. Cer: Ceramide; SM: Sphingomyelin; DhCer: Dihydroceramide; HexCer: Hexosylceramide; LacCer: Lactosylceramide; Sph: Sphingosine; S1P: Sphingosine-1-phosphate; Spa: Sphinganine; Spa1P: Sphinganine-1-phosphate.