Content area
Full text
Article info
Article History:
Received: 4 June 2016
Accepted: 9 June 2017
epublished: 29 June 2017
Keywords:
Adipose Tissue
Cholesterol
HDL-C
Ileum
Statins
Abstract
Hydroxy-Methyl-Glutaryl-CoA reductase (HMGCR) - the main enzyme of the cholesterol biosynthesis pathway - is mostly inhibited by statins in hepatocytes. In spite of the other tissues, liver utilizes cholesterol in different ways such as the synthesis of bile acids, excretion in to the intestine and synthesis of lipoproteins. Therefore, statins theoretically alter these pathways; although, there have not been such effects. In this review, we aim to show the roles of extra-hepatic tissues, in particular intestine, adipose and cutaneous tissues in providing the cholesterol after reduction of the whole body cholesterol content by statins.
Introduction
Cholesterol absorption in the small intestine and cholesterol synthesis in hepatic and extra-hepatic tissues contribute to maintaining cholesterol homeostasis in the body. Our body loses at least 900 mg cholesterol daily and this must be compensated through diet or de novo synthesis in the body.1
Cholesterol metabolism in the liver
Not only dietary cholesterol is directly transported to the liver, hepatocytes also synthesize about 60%-70% of the whole body cholesterol.2
Cholesterol is precursor to bile acids in the liver, steroid hormones in steroidogenic organs and Vitamin-D in subcutaneous tissue.3 Regarding the vital roles of cholesterol, inhibition of the cholesterol biosynthesis by statins without providing cholesterol for liver may result in inefficiency of liver.
Induction of reverse cholesterol transport (RCT) process which transfers the excess amounts of cholesterol from extra-hepatic tissues to liver and also increase in the cholesterol absorption level in the intestine can be considered as the main ways of compensation of the cholesterol insufficiency in the liver at the result of statin therapy.
Except for liver, some tissues and cells have a remarkable role in cholesterol metabolism; these include gastrointestinal tract, adipose tissue and macrophages. The role of these tissues and cells in cholesterol metabolism have been shown in the next.
Statins induce the component of RCT
Since there is a permanent cholesterol exchange between serum and tissues, the cholesterol of different tissues originates either from in situ synthesis or serum.4 Therefore, serum and other tissues can be considered as cholesterol sources for liver and vice versa. Peripheral cells (apart from steroidogenic and...