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.

Physiological and pharmacokinetic effects of multilevel caging on Sprague Dawley rats under ketamine-xylazine anesthesia

“…Cytochrome P450 expression and function are influenced by obesity levels, such as CYP3A hepatic expression levels are increased in high-fat fed Sprague-Dawley rats [14], whereas decreased activity has previously been linked to obesity in humans [4]. In addition, liver transcriptomics analysis of mouse induced obesity models revealed a global dysregulation of Cyp genes, most notably in the Cyp3a and Cyp2c families [11]. Similar changes were also observed in diet-induced metabolic syndrome in guinea pigs, where decreases CYP3A expression and activity were observed in high-fat high-sucrose and high-fat high-fructose diets [25].…”

Induction of Steatohepatitis (NASH) with Insulin Resistance in Wild-type B6 Mice by a Western-type Diet Containing Soybean Oil and Cholesterol

“…Neither TNFα nor cholesterol alone enhanced actinomycin D-stimulated caspase 3 activity significantly. However, if mouse hepatocytes were exposed to a combination of TNFα and cholesterol, the actinomycin D-dependent caspase 3 activity was significantly increased about two-fold ( Figure 6C) and there was a significant interaction between cholesterol and TNFα (two-way analysis of variance, obesogenic, diabetogenic and proinflammatory than fat sources such as lard or coconut oil with saturated fatty acids or fish oil with a different PUFA composition (13,14,(37)(38)(39). The high content of n-6-PUFA in soybean oil exaggerated insulin resistance and increased liver steatosis and inflammation in mice (38,14), while a high n-3/n-6-PUFA ratio in the diet reduced hepatic steatosis in humans and mice (39)(40)(41).…”

“…However, in contrast to patients suffering from the metabolic syndrome, animals fed a cholinemethionine-deficient diet lose weight and are not insulin resistant (10). When added to a high-fat diet, both fructose (11) and cholesterol (12) as well as increased n-6-polyunsaturated fatty acid (n-6-PUFA) in the fat content (13,14) seem to favor development of liver steatosis and insulin resistance or inflammation and fibrosis. Therefore, in the current study, three high-fat diets differing in their fatty acid composition as well as cholesterol and fructose content were compared for their impact on weight gain, insulin resistance and development of NASH.…”

Mediterranean Diet and Prevention of Chronic Diseases

“…Clearly, a major tenet of the MD eating pattern is that fats present in olive oil (18:1) and fish (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) should not be equated to those present in vegetable oils rich in n-6 LA for which obesogenic and diabetogenic effects have been observed in some preclinical studies. 20 In general, results from clinical, cross-sectional, and prospective studies support the health benefits of a MD eating pattern against MetS. The clinical diagnosis of MetS is having at least three of the following conditions: a waist circumference 9 102 cm for men and 9 88 cm for women; high TG levels (Q150 mg/dL); low HDL-C (G40 mg/dL for men and G50 mg/dL for women); high blood pressure (BP Q130/85 mmHg) on at least two separate measurements; and high fasting glucose (Q100 mg/dL or Q5.6 mmol/L).…”