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Omega-6 and omega-3 oxylipins are implicated in soybean oil-induced obesity in mice (part IV)

ABSTRACT: In this study we have compared the metabolic effects of conventional soybean oil to those of genetically modified Plenish soybean oil, that is low in linoleic acid and high in oleic acid. This work builds on our previous study showing that soybean oil, rich in polyunsaturated fats, is more obesogenic and diabetogenic than coconut oil, rich in saturated fats (PMID: 26200659). Here, in order to elucidate the mechanisms responsible for soybean oil induced obesity, we have performed the first ever metabolomics (in plasma and liver) and proteomics on the livers of mice fed the two soybean oil diets (plus those fed a high coconut oil and Viv chow diet). Our results show that the new high oleic soybean oil induces less obesity and adiposity than conventional soybean oil, but can cause hepatomegaly and liver dysfunction. Metabolomic analysis reveals that the hepatic and plasma metabolic profiles differ considerably between the two soybean oils. Hepatic C18 oxylipin metabolites of omega-6 (ω6) and omega-3 (ω3) fatty acids (linoleic and α-linolenic acid, respectively) in the cytochrome P450/soluble epoxide hydrolase pathway were found to correlate positively with obesity.

ORGANISM(S): Mouse Mus Musculus

TISSUE(S): Blood

DISEASE(S): Obesity

SUBMITTER: Oliver Fiehn

PROVIDER: ST000658 | MetabolomicsWorkbench | Fri Jun 23 00:00:00 BST 2017

REPOSITORIES: MetabolomicsWorkbench

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Project description:Elevated circulating lipid levels are known risk factors for cardiovascular diseases (CVD). In order to examine the effects of quercetin on hepatic lipid metabolism and detailed serum lipid profiles, mice received a mild-high-fat diet without (control) or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Gas chromatography and 1H nuclear magnetic resonance were used to measure quantitatively serum lipid profiles and whole genome microarray analysis was used to identify the responsible mechanisms in liver. There were no significant differences found in mean body weight, energy intake and hepatic lipid accumulation between the quercetin and control group. In serum of quercetin-fed mice, TG levels were decreased with 15%, poly unsaturated fatty acids (PUFA) were increased with 14% and saturated fatty acids were decreased. Palmitic acid, oleic acid, and linoleic acid were all decreased in quercetin-fed mice by 9-15%. Both palmitic acid and oleic acid can be oxidized by omega-oxidation. Indeed, gene expression profiling showed that quercetin increased hepatic lipid metabolism, especially omega-oxidation. At the gene level, this was reflected by the up regulation of cytochrome P450 (Cyp) 4a10, Cyp4a14, Cyp4a31 and Acyl-CoA thioesterase 3 (Acot3). Two relevant regulators, Cytochrome P450 oxidoreductase (Por, rate limiting for cytochrome P450s) and the transcription factor Constitutive androstane receptor (Car; official symbol Nr1i3) were also up regulated in the quercetin-fed mice. We conclude that quercetin intake increased hepatic lipid omega-oxidation and lowered corresponding circulating lipid levels, a process that may involve Por and Car, and results in a potential beneficial CVD preventive effect. Liver samples were obtained from 36 C57BL/6J male adult mice. All mice started with a three week adaptation phase, in which they were fed a mild-high-fat diet. 12 mice were sacrificed immediately after the adaptation phase (t=0). The other 24 mice received the mild-high-fat diet without (HF) or with supplementation of 0.33% (w/w) quercetin (HF-Q) for 12 weeks.

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Omega-6 and omega-3 oxylipins are implicated in soybean oil-induced obesity in mice (part IV)

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