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.

Highlights

  • While humans have been cultivating soybeans for ~5000 years[1], soybean oil has become a substantial part of our diet only in the last few decades[2]

  • These results indicate that the fatty liver phenotype does not always track with obesity, diabetes or insulin resistance. They show that the genetic modification of soybean oil may induce detrimental health effects in terms of liver function even though it induces less obesity and insulin resistance than conventional soybean oil. This is the first report to compare the metabolic effects of conventional soybean oil to those of genetically modified (GM) oil (Plenish) with low linoleic acid (LA) but high oleic acid

  • It is the first study to compare the metabolomic and proteomic profiles induced by these oils high in unsaturated fats to those generated by an oil rich in saturated fatty acids

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Summary

Introduction

While humans have been cultivating soybeans for ~5000 years[1], soybean oil has become a substantial part of our diet only in the last few decades[2] This increase in soybean oil consumption is due in part to a reaction to large-scale population studies in the 1950s and 60s, which showed that a typical American diet rich in saturated fats from animal products was linked to an increased risk of cardiovascular disease[3,4]. While most experimental diet-induced obesity studies use high fat diets composed of lard or milk fat (rich in saturated fats), a few recent studies (including one from our group) have examined the effects of a diet rich in soybean oil and found that this vegetable oil does increase adiposity, diabetes, insulin resistance and fatty liver[9,13,14,15]. Extensive metabolomic and proteomic analyses indicate that oxylipin metabolites of LA and α-linolenic acid (ALA, C18:3ω3) correlate positively with obesity

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