title: Soybean Oil Is More Obesogenic and Diabetogenic than Coconut Oil and Fructose in Mouse: Potential Role for the Liver.
abstract: The obesity epidemic in the U.S. has led to extensive research into potential contributing dietary factors, especially fat and fructose. Recently, increased consumption of soybean oil, which is rich in polyunsaturated fatty acids (PUFAs), has been proposed to play a causal role in the epidemic. Here, we designed a series of four isocaloric diets (HFD, SO-HFD, F-HFD, F-SO-HFD) to investigate the effects of saturated versus unsaturated fat, as well as fructose, on obesity and diabetes. C57/BL6 male mice fed a diet moderately high in fat from coconut oil and soybean oil (SO-HFD, 40% kcal total fat) showed statistically significant increases in weight gain, adiposity, diabetes, glucose intolerance and insulin resistance compared to mice on a diet consisting primarily of coconut oil (HFD). They also had fatty livers with hepatocyte ballooning and very large lipid droplets as well as shorter colonic crypt length. While the high fructose diet (F-HFD) did not cause as much obesity or diabetes as SO-HFD, it did cause rectal prolapse and a very fatty liver, but no balloon injury. The coconut oil diet (with or without fructose) increased spleen weight while fructose in the presence of soybean oil increased kidney weight. Metabolomics analysis of the liver showed an increased accumulation of PUFAs and their metabolites as well as γ-tocopherol, but a decrease in cholesterol in SO-HFD. Liver transcriptomics analysis revealed a global dysregulation of cytochrome P450 (Cyp) genes in SO-HFD versus HFD livers, most notably in the Cyp3a and Cyp2c families. Other genes involved in obesity (e.g., Cidec, Cd36), diabetes (Igfbp1), inflammation (Cd63), mitochondrial function (Pdk4) and cancer (H19) were also upregulated by the soybean oil diet. Taken together, our results indicate that in mice a diet high in soybean oil is more detrimental to metabolic health than a diet high in fructose or coconut oil.
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside, Riverside, California, United States of America.
authors.forename: Poonamjot
authors.initials: P
authors.lastname: Deol
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside, Riverside, California, United States of America.
authors.forename: Jane R
authors.initials: JR
authors.lastname: Evans
authors.affiliation: Department of Biochemistry, University of California, Riverside, Riverside, California, United States of America.
authors.forename: Joseph
authors.initials: J
authors.lastname: Dhahbi
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside, Riverside, California, United States of America.
authors.forename: Karthikeyani
authors.initials: K
authors.lastname: Chellappa
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside, Riverside, California, United States of America.
authors.forename: Diana S
authors.initials: DS
authors.lastname: Han
authors.affiliation: Department of Biochemistry, University of California, Riverside, Riverside, California, United States of America.
authors.forename: Stephen
authors.initials: S
authors.lastname: Spindler
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside, Riverside, California, United States of America.
authors.forename: Frances M
authors.initials: FM
authors.lastname: Sladek
mesh_terms: D000818:Animals; D000074263:Coconut Oil; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D004041:Dietary Fats / Q000009:adverse effects; D005632:Fructose / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D009765:Obesity / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D010938:Plant Oils / Q000009:adverse effects*; D013024:Soybean Oil / Q000009:adverse effects*
chemical_list: D004041:Dietary Fats; D010938:Plant Oils; D005632:Fructose; D013024:Soybean Oil; D003577:Cytochrome P-450 Enzyme System; D000074263:Coconut Oil