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.
Highlights
There has been an alarming increase in obesity and its associated co-morbidities—diabetes and heart disease—in the U.S during the last four decades
In order to compare the effects of a diet enriched in soybean oil to one consisting primarily of saturated fat from coconut oil, and to examine the effects of fructose, we designed four isocaloric diets: high fat diet (HFD, 40 kcal% fat, primarily from coconut oil), soybean oil-enriched HFD (SO-HFD), fructose-enriched HFD (F-HFD) and fructose-enriched SO-HFD (F-SO-HFD) (Table 1)
Coconut oil, which consists mainly of saturated fats of chain length 12 to 18 (Table 2), was used as the primary source of fat as it is naturally low in LA and other polyunsaturated fatty acids (PUFAs), whereas diets made from lard can have variable amounts of PUFAs depending on what the animals have been fed [24,53,54]
Summary
There has been an alarming increase in obesity and its associated co-morbidities—diabetes and heart disease—in the U.S during the last four decades. Nutritional guidelines were developed that encouraged people to reduce their intake of saturated fat, typically found in meat and dairy products, and increase their intake of polyunsaturated fatty acids (PUFAs) found in plant oils [8,9]. These guidelines are still in effect today [10]. There is a growing body of evidence that suggests that saturated fat from sources such as coconut and palm oil, which are rich in medium chain triglycerides (MCTs), may be beneficial for the prevention and treatment of the Metabolic Syndrome [13,14,15]
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