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.