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Nuclear receptors comprise a superfamily of ligand-activated transcription factors that are involved in important aspects of hepatic physiology and pathophysiology. There are about 48 nuclear receptors in the human. These nuclear receptors are regulators of many hepatic processes including hepatic lipid and glucose metabolism, bile acid homeostasis, drug detoxification, inflammation, regeneration, fibrosis, and tumor formation. Some of these receptors are sensitive to the levels of molecules that control lipid metabolism including fatty acids, oxysterols, and lipophilic molecules. These receptors direct such molecules to the transcriptional networks and may play roles in the pathogenesis and treatment of nonalcoholic fatty liver disease. Understanding the mechanisms underlying the involvement of nuclear receptors in the pathogenesis of nonalcoholic fatty liver disease may offer targets for the development of new treatments for this liver disease.

The prevalence of metabolic syndrome is growing around the world at an alarming rate. Obesity involves a plethora of molecules that predispose individuals to an inflammatory state and various metabolic complications. Dysregulation of nutrient metabolism is a key step during the progression of chronic liver disease that induces an inflammatory state, cellular damage, and impaired hepatic insulin signaling, which leads to insulin resistance. Insulin resistance arises from multiple defects in the liver, adipose tissues, and muscle signaling, which leads to a failure to suppress hepatic gluconeogenesis and glycogenolysis, thereby enhancing fat accumulation in the hepatocytes via increased lipolysis and increased hepatic synthesis of triglycerides. This metabolic condition also increases the frequency of other comorbidities such as liver and biliary diseases. Nonalcoholic fatty liver disease is the hepatic expression of metabolic syndrome, which comprises a spectrum of clinical and histological events ranging from simple and benign fatty liver to steatohepatitis, which is characterized by the abnormal activation of pathways leading to an aggressive inflammatory condition. This pathological state may progress to more severe damage known as cirrhosis, which endangers the anatomy and function of liver tissue. In addition, a small group of patients with end-stage liver disease may develop hepatocellular carcinoma and finally death. By contrast, cholesterol gallstone disease is a common metabolic disease, and is considered to be the main biliary indicator of metabolic syndrome. This review provides a detailed summary of the hepatic manifestations associated with metabolic syndrome. Copyright © 2013 John Wiley & Sons, Ltd.

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