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Omega-6 and omega-3 oxylipins are implicated in soybean oil-induced obesity in mice.

ABSTRACT: Soybean oil consumption is increasing worldwide and parallels a rise in obesity. Rich in unsaturated fats, especially linoleic acid, soybean oil is assumed to be healthy, and yet it induces obesity, diabetes, insulin resistance, and fatty liver in mice. Here, we show that the genetically modified soybean oil Plenish, which came on the U.S. market in 2014 and is low in linoleic acid, induces less obesity than conventional soybean oil in C57BL/6 male mice. Proteomic analysis of the liver reveals global differences in hepatic proteins when comparing diets rich in the two soybean oils, coconut oil, and a low-fat diet. Metabolomic analysis of the liver and plasma shows a positive correlation between obesity and 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. While Plenish induced less insulin resistance than conventional soybean oil, it resulted in hepatomegaly and liver dysfunction as did olive oil, which has a similar fatty acid composition. These results implicate a new class of compounds in diet-induced obesity-C18 epoxide and diol oxylipins.

SUBMITTER: Deol P

PROVIDER: S-EPMC5624939 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Omega-6 and omega-3 oxylipins are implicated in soybean oil-induced obesity

Project description:Soybean oil consumption is increasing worldwide and parallels the obesity epidemic in the U.S. Rich in unsaturated fats, especially linoleic acid, soybean oil is assumed to be healthy, and yet it induces obesity, diabetes, insulin resistance and fatty liver in mice. The genetically modified soybean oil Plenish came on the U.S. market in 2014: it is low in linoleic acid and similar to olive oil in fatty acid composition. Here we show that Plenish induces less obesity than conventional soybean oil: metabolomics, proteomics and a transgenic mouse model implicate oxylipin metabolites of omega-6 and omega-3 fatty acids (linoleic and α-linolenic acid, respectively), which are generated by target genes of nuclear receptor HNF4α. While Plenish induces less insulin resistance than conventional soybean oil, it results in hepatomegaly and liver dysfunction as does olive oil. Altering the fatty acid profile of soybeans could help reduce obesity but may also cause liver complications.

2017-03-20 | GSE79408 | GEO

Omega-6 and omega-3 oxylipins are implicated in soybean oil-induced obesity in mice

Project description:Soybean oil consumption is increasing worldwide and parallels the rise in obesity. Rich in unsaturated fats, especially linoleic acid, soybean oil is assumed to be healthy, and yet it induces obesity, diabetes, insulin resistance and fatty liver in mice. Here, we show that the genetically modified soybean oil Plenish, which came on the U.S. market in 2014 and is low in linoleic acid, induces less obesity than conventional soybean oil in C57BL/6male mice.

2017-06-08 | MSV000081149 | MassIVE

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

Project description: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.

2017-06-23 | ST000658 | MetabolomicsWorkbench

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

2017-06-23 | ST000656 | MetabolomicsWorkbench

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

2017-06-22 | ST000660 | MetabolomicsWorkbench

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

2017-06-22 | ST000655 | MetabolomicsWorkbench

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

Project description:Characterization and analysis of metabolomic, proteomic and metabolic profiles of C57/Bl6N mice fed various high fat diets

2017-07-26 | ST000901 | MetabolomicsWorkbench

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

Project description:Characterization and analysis of metabolomic, proteomic and metabolic profiles of C57/Bl6N mice fed various high fat diets

2017-07-26 | ST000902 | MetabolomicsWorkbench

Omega-6 and omega-3 oxylipins as potential markers of cardiometabolic risk in young adults.

Project description:ObjectiveOmega-6 and omega-3 oxylipins are known to play a role in inflammation and cardiometabolic diseases in preclinical models. The associations between plasma levels of omega-6 and omega-3 polyunsaturated fatty acid-derived oxylipins and body composition and cardiometabolic risk factors in young adults were assessed.MethodsBody composition, brown adipose tissue, traditional serum cardiometabolic risk factors, inflammatory markers, and a panel of 83 oxylipins were analyzed in 133 young adults (age 22.1[SD 2.2] years, 67% women).ResultsPlasma levels of four omega-6 oxylipins (15-HeTrE, 5-HETE, 14,15-EpETrE, and the oxidative stress-derived 8,12-iso-iPF2α -VI) correlated positively with adiposity, prevalence of metabolic syndrome, fatty liver index, and homeostatic model assessment of insulin resistance index and lipid parameters. By contrast, the plasma levels of three omega-3 oxylipins (14,15-DiHETE, 17,18-DiHETE, and 19,20-DiHDPA) were negatively correlated with adiposity, prevalence of metabolic syndrome, fatty liver index, homeostatic model assessment of insulin resistance index, and lipid parameters. The panel of seven oxylipins predicted adiposity better than traditional inflammatory markers such as interferon gamma or tumor necrosis factor-alpha. Pathway analyses revealed that individuals with obesity had higher plasma levels of omega-6 and lower plasma levels of omega-3 oxylipins than normal-weight individuals.ConclusionPlasma levels of seven omega-6 and omega-3 oxylipins may have utility as early markers of cardiometabolic risk in young adults.

| S-EPMC9299871 | biostudies-literature

Human CYP2B6 produces oxylipins from polyunsaturated fatty acids and reduces diet-induced obesity.

Project description:Multiple factors in addition to over consumption lead to obesity and non-alcoholic fatty liver disease (NAFLD) in the United States and worldwide. CYP2B6 is the only human detoxification CYP whose loss is associated with obesity, and Cyp2b-null mice show greater diet-induced obesity with increased steatosis than wildtype mice. However, a putative mechanism has not been determined. LC-MS/MS revealed that CYP2B6 metabolizes PUFAs, with a preference for metabolism of ALA to 9-HOTrE and to a lesser extent 13-HOTrE with a preference for metabolism of PUFAs at the 9- and 13-positions. To further study the role of CYP2B6 in vivo, humanized-CYP2B6-transgenic (hCYP2B6-Tg) and Cyp2b-null mice were fed a 60% high-fat diet for 16 weeks. Compared to Cyp2b-null mice, hCYP2B6-Tg mice showed reduced weight gain and metabolic disease as measured by glucose tolerance tests, however hCYP2B6-Tg male mice showed increased liver triglycerides. Serum and liver oxylipin metabolite concentrations increased in male hCYP2B6-Tg mice, while only serum oxylipins increased in female hCYP2B6-Tg mice with the greatest increases in LA oxylipins metabolized at the 9 and 13-positions. Several of these oxylipins, specifically 9-HODE, 9-HOTrE, and 13-oxoODE, are PPAR agonists. RNA-seq data also demonstrated sexually dimorphic changes in gene expression related to nuclear receptor signaling, especially CAR > PPAR with qPCR suggesting PPARγ signaling is more likely than PPARα signaling in male mice. Overall, our data indicates that CYP2B6 is an anti-obesity enzyme, but probably to a lesser extent than murine Cyp2b's. Therefore, the inhibition of CYP2B6 by xenobiotics or dietary fats can exacerbate obesity and metabolic disease potentially through disrupted PUFA metabolism and the production of key lipid metabolites.

| S-EPMC9754190 | biostudies-literature

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