Abstract
Bile acids are amphipathic molecules synthesized from cholesterol in the liver. Bile acid synthesis is a major pathway for hepatic cholesterol catabolism. Bile acid synthesis generates bile flow which is important for biliary secretion of free cholesterol, endogenous metabolites, and xenobiotics. Bile acids are biological detergents that facilitate intestinal absorption of lipids and fat-soluble vitamins. Recent studies suggest that bile acids are important metabolic regulators of lipid, glucose, and energy homeostasis. Agonists of peroxisome proliferator-activated receptors (PPARα, PPARγ, PPARδ) regulate lipoprotein metabolism, fatty acid oxidation, glucose homeostasis and inflammation, and therefore are used as anti-diabetic drugs for treatment of dyslipidemia and insulin insistence. Recent studies have shown that activation of PPARα alters bile acid synthesis, conjugation, and transport, and also cholesterol synthesis, absorption and reverse cholesterol transport. This review will focus on the roles of PPARs in the regulation of pathways in bile acid and cholesterol homeostasis, and the therapeutic implications of using PPAR agonists for the treatment of metabolic syndrome.
Highlights
Fibrates have been used for decades to treat hypertriglyceridemia or mixed hyperlipidemia for their ability to significantly reduce plasma triglyceride levels [1]
The roles of PPARs have been extended from stimulating fatty acid oxidation and glucose metabolism to regulating cholesterol and lipoprotein metabolism, bile acid metabolism, energy homeostasis and inflammation, and so forth
Most of the regulatory roles of PPARs turned out to be beneficial in improving dyslipidemia and glucose homeostasis and reducing the risks of major cardiovascular and heart events, while others may represent adverse effects associated with the use of certain PPAR agonists
Summary
Fibrates have been used for decades to treat hypertriglyceridemia or mixed hyperlipidemia for their ability to significantly reduce plasma triglyceride levels [1]. PPARα regulates a network of genes that promote lipolysis and fatty acid β-oxidation, the major mechanisms mediating the lipid lowering effects of fibrates. PPARδ plays a role in fatty acid and energy metabolism in the muscle. The transport of bile acids between liver and intestine is referred to as the enterohepatic circulation of bile, which plays important roles in liver function, liver physiology, and metabolic regulation. The liver plays a central role in maintaining cholesterol homeostasis by balancing multiple pathways including de novo cholesterol and bile acid synthesis, dietary. This review will summarize the recent development in understanding the role of PPARs in regulation of bile acid and cholesterol homeostasis, and the therapeutic implications in using PPAR agonists for treating metabolic dyslipidemia and reducing the risk of cardiovascular and heart diseases
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