AJP - Endocrinology and Metabolism, Vol 263, Issue 2 E287-E295, Copyright © 1992 by American Physiological Society

ARTICLES

Is there a role for the adrenals in the development of hypercholesterolemia in Zucker fatty rats?

F. Alarrayed, A. D. Hartman and J. R. Porter
Department of Physiology, Louisiana State University Medical Center, New Orleans 70119.

We tested the hypothesis that hypercorticosteronemia causes the hypercholesterolemia in young developing "fatty" rats. Obesity induced increases in corticosterone. Insulin, glucose, body weight, average daily food intake, plasma triglyceride, plasma phospholipids, liver weight, liver triglyceride, various adipose tissue parameters, and liver hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity were all ameliorated by adrenalectomy. Adrenalectomy exacerbated the hypercholesterolemia in obese animals and induced it in lean rats. Changes or lack of change in hepatic microsomal cholesterol, HMG-CoA reductase, and 7 alpha-hydroxylase, combined with the adrenalectomy-induced curtailment of tissue storage of cholesterol in adipose tissue, all contribute to the hypercholesterolemia caused by adrenalectomy. We suggest a mechanism whereby this may be related to elevated hepatic very low-density lipoprotein secretion rates. The elevated HMG-CoA reductase activity in obese rats results from the lower liver microsomal free cholesterol content. We conclude that the absence of glucocorticoids does not directly reduce plasma cholesterol in obese Zucker rats. The surprising elevation of cholesterol by adrenalectomy is due to other prevailing mechanisms in liver and adipose tissue, which curtail their capacity to store cholesterol.

This article has been cited by other articles:

				J. C. Clapham and N. C. Turner Effects of the Glucocorticoid II Receptor Antagonist Mifepristone on Hypertension in the Obese Zucker Rat J. Pharmacol. Exp. Ther., September 1, 1997; 282(3): 1503 - 1508. [Abstract] [Full Text]