Studies on the etiology of increased tissue cholesterol concentration in cholesterol-fed hypothyroid rats

Hypothyroid rats fed an atherogenic diet (A) for 3 weeks developed a marked hyperlipidemia characterized by elevated very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol. Cholesterol concentrations of adipose tissue, liver, carcass and soleus muscle were significantly increased in rats fed the A diet versus rats fed a control diet (C). After 5 months on the A diet, cholesterol concentrations of adipose tissue, carcass and soleus muscle were not different from those measured in rats fed the A diet for 3 weeks; however, liver cholesterol concentration was 20-fold higher. To study the mechanisms by which the A diet increased adipocyte cholesterol content, in vitro binding studies were conducted with normal (N) and cholesterol enriched (CH) 125I-labeled VLDL. The inability of unlabeled N and CH VLDL to displace 125I-labeled VLDL supports the concept that VLDL was not specifically bound by rat adipocytes. The observation that adipocyte and other tissue cholesterol levels were similar at 3 weeks and 5 months suggests regulation of tissue cholesterol concentrations. The mechanism of regulation of adipocyte cholesterol was not related to VLDL binding or differential binding rates between N and CH VLDL.