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Studies on the Etiology of Increased Tissue Cholesterol Concentration in Cholesterol-Fed Hypothyroid Rats¹

P. M. Kris-Etherton^*, Mary Ann Fosmire^*, D. J. Mela^* and Terry D. Etherton

^* Nutrition Program Department of Dairy and Animal Science, The Pennsylvania State University, University Park, PA 16802

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.

KEY WORDS: • hyperlipidemia • hypothyroidism • cholesterol metabolism • lipoprotein composition and metabolism • tissue cholesterol • adipocyte • soleus muscle

¹ Supported by Biomedical Research Support Grants RR07082-13 and RR07082-14 (National Institutes of Health) and The American Heart Association. Pennsylvania Affiliate. This work was presented in part at the annual meetings of the Federation of American Societies for Experimental Biology in Atlanta. April, 1981, and published in abstract form in Fed. Proc. 40, 688. 1981. This manuscript was authorized for publication as paper no. 6478 in the journal series of The Pennsylvania Agricultural Experiment Station.

Manuscript received 16 June 1982.