Liver X receptors: new drug targets to treat Type 2 diabetes?

Obesity and dyslipidemia are both risk factors for developing Type 2 diabetes and cardiovascular disease (CVD). These diseases have become a major health hazard in society; 177 million people suffered from diabetes worldwide in 2000 and this number will increase to at least 300 million by 2025. Type 2 diabetes and CVD are most probably of polygenetic origin and research has focused primarily on understanding regulation of lipid, cholesterol and glucose metabolism to elucidate the pathophysiology of these diseases. Liver X receptors are important regulators of fatty acid biosynthesis and cholesterol and glucose metabolism. They regulate transcription of key genes involved in several metabolic processes, including cytochrome P450 7A1, ATP binding cassette-lipid/cholesterol transporters, sterol regulatory element binding protein-1c and glucose transporter 4. Hence, liver X receptors promote reverse cholesterol transport, conversion of cholesterol to bile acids, reduced absorption of cholesterol in the intestines, increased triglyceride synthesis with hypertriglycericlemia as a consequence, reduced hepatic glucose production and increased glucose uptake in peripheral tissues, Liver X receptors have emerged as highly interesting drug targets to treat obesity and dyslipiclemia, and subsequently Type 2 diabetes and CVD.