High-fructose and high-fat diet-induced insulin resistance enhances atherosclerosis in Watanabe heritable hyperlipidemic rabbits

Bo Ning, Xiaoyan Wang, Ying Yu, Ahmed Bilal Waqar, Qi Yu, Tomonari Koike, Masashi Shiomi, Enqi Liu, Yifei Wang, Jianglin Fan

Individuals with insulin resistance and resulting impaired glucose tolerance along with type 2 diabetes showed an increased prevalence of atherosclerosis. Our aim in this study was to address whether diet-induced insulin resistance plays any roles in the development of aortic and coronary atherosclerosis in hyperlipidemic rabbits. We fed Watanabe heritable hyperlipidemic (WHHL) rabbits with a high-fructose and high-fat diet (HFFD) with restricted normal calories and compared the lesions of both aortic and coronary atherosclerosis with those of control WHHL rabbits fed a normal chow diet. HFFD-fed WHHL rabbits showed insulin resistance and impaired glucose tolerance accompanied by elevated plasma lipid levels and accumulation of adipose tissue even though their body weight was unchanged compared to the control rabbits. At 8 weeks, the aortic gross lesion area of HFFD-fed WHHL rabbits was increased by 40 % over the controls and their lesions were characterized by increased number of macrophages and smooth muscle cells. At 16 weeks, the lesions of HFFD-fed WHHL rabbits showed more advanced lesions such as lipid core formation and calcification. In addition, coronary atherosclerosis was significantly increased in HFFD-fed WHHL rabbits. These results suggest that insulin resistance accelerates lesion formation of atherosclerosis.