Multiple time‐dependent pathophysiological changes in a rabbit model of high‐fat diet‐induced hyperlipidemia

Abstract

High‐fat diets (HFD) adversely affect organ systems. Several studies have examined HFD‐related disorders in animals but only in a few organs and time points. Herein, we evaluated disease development with time‐dependent HFD‐induced pathological, cardiovascular, and morphological changes in rabbits with lipid metabolism similar to that in humans for 9 weeks. The body weights and waist ratio of the HFD group were higher than those in the control group. HFD significantly increased the total cholesterol, low‐density lipoprotein, high‐density lipoprotein, and phospholipid levels after 3 weeks. Liver enzyme levels increased with hepatomegaly, steatosis, and fibrosis after 3 or 6 weeks. RBCs and hemoglobin decreased, while platelets increased in the HFD group with atherosclerosis and inflammatory cell infiltration in the aorta after 6 weeks. Ejection fraction and fractional shortening values decreased in the HFD group after 9 weeks. Creatinine increased with glomerulosclerosis in the kidneys of the HFD groups after 3 weeks, indicating renal dysfunction. Lipid accumulation was found in the pancreas after 9 weeks. Lipid accumulation and hypertrophy were observed in the adrenal glands after 3 weeks. Overall, our findings provide global reference data on the time‐dependent effects of HFD on the body and may serve as a guide for future HFD risk prevention.