Gluten exacerbates atherosclerotic plaque formation in ApoE–/– mice with diet-induced obesity

Abstract

Objectives Atherosclerosis is an underlying cause of cardiovascular disease, and obesity is one of the risk factors for atherogenesis. Although a gluten-free diet (GFD) has gained popularity as a strategy for weight loss, little is known about the effects of gluten on obesity. We have previously shown a negative effect of gluten on obesity in mice. However, its effects on atherogenesis are still unknown. Therefore, the aim of this study was to determine the effects of gluten on atherosclerosis progression during obesity. Methods Atherosclerosis-susceptible ApoE knockout mice were subjected to an obesogenic GFD or a diet with 4.5% gluten (GD) for 10 wk. Results Results from the study found that food intake and lipid profile were similar between the groups. However, GD promoted an increase in weight gain, adiposity, and plasma glucose. Pro-inflammatory factors such as tumor necrosis factor, interleukin-6, chemokine ligand-2, and matrix metalloproteinase-2 and -9 also were increased in the adipose tissue of gluten-fed mice. This inflammatory profile was associated with reduced phosphorylation of Akt, and consequently with the intensification of insulin resistance. The GD-enhanced vascular inflammation contributed to the worsening of atherosclerosis in the aorta and aortic root. Inflammatory cells, such as monocyte/macrophage and natural killer cells, and oxidative stress markers, such as superoxide and nitrotyrosine, were increased in atherosclerotic lesions of the GD group. Furthermore, the lesions presented higher necrotic core and lower collagen content, characterizing the less stable plaques. Conclusion The gluten-containing high-fat diet was associated with a more severe proatherogenic profile than the gluten-free high-fat diet owing to increased inflammatory and oxidative status at atherosclerotic lesions in obese mice.