Dynamics of hepatic and intestinal cholesterol and bile acid pathways: The impact of the animal model of estrogen deficiency and exercise training

Abstract

Plasma cholesterol level is determined by a complex dynamics that involves transport lipoproteins which levels are tightly dependent on how the liver and the intestine regulate cholesterol and biliary acid metabolism. Regulation of cholesterol and biliary acids by the liver and the intestine is in turn coupled to a large array of enzymes and transporters that largely influence the inflow and the outflow of cholesterol and biliary acids through these organs. The activity of the key regulators of cholesterol and biliary acids may be influenced by several external factors such as pharmacological drugs and the nutritional status. In recent years, more information has been gathered about the impact of estrogens on regulation of cholesterol in the body. Exposure to high levels of estrogens has been reported to promote cholesterol gallstone formation and women are twice as likely as men to develop cholesterol gallstones. The impact of estrogen withdrawal, such as experienced by menopausal women, is therefore of importance and more information on how the absence of estrogens influence cholesterol regulation is started to come out, especially through the use of animal models. An interesting alternative to metabolic deterioration due to estrogen deficiency is exercise training. The present review is intended to summarize the present information that links key regulators of cholesterol and biliary acid pathways in liver and intestine to the absence of estrogens in an animal model and to discuss the potential role of exercise training as an alternative.

Keywords: PSCK9; Low-density lipoprotein receptor; Very low-density lipoprotein; Sterol regulatory element binding proteins; Ovariectomy; High-density lipoprotein; Lipoproteins

Core tip: The liver is considered the master piece in regulation of plasma cholesterol levels. Together with the intestine they control the influx and the efflux of cholesterol and biliary acids in the body. Cholesterol and its conversion into biliary acids are regulated by an extended network of enzymes and transporters that largely influence plasma cholesterol levels. The key regulators of cholesterol and biliary acids in liver and intestine are in turn affected by several factors including estrogens levels and more recently exercise training. Low estrogenic levels, such as seen in post-menopausal women, are associated with higher plasma cholesterol levels. In recent years more information has been accumulated on the extent to which low estrogenic levels, such as seen in an ovariectomized animal model, influence cholesterol and biliary metabolism at the molecular level. As an alternative to a deficiency in estrogens, exercise training has been reported to exert a beneficial effect on these key regulators of cholesterol and biliary acids.