[New heterodimeric nuclear receptors: key metabolic regulators with relevance in the pathophysiology and therapy of dyslipidemias and diabetes mellitus].
The regulation of gene expression is crucial for the normal development and the homeostatic maintenance of body tissues. Thus, its malfunction may determine a variety of human disease conditions. A growing body of evidence has shown the overwhelming relevance of a new class of gene expression regulators: the heterodimeric nuclear receptors, a family of structurally related proteins involved in multiple biological functions. In response to activating ligands, these molecules bind to specific genomic regulatory regions where they can coordinately modify the transcriptional activity of several genes involved in the main metabolic pathways of lipids and carbohydrates in cells. These functional properties have stimulated the study of the relationships between heterodimeric nuclear receptors and various disease conditions, such as dyslipidemias and diabetes mellitus. Here we review the experimental, clinical and epidemiological evidences that support the relevance of these transcriptional regulators in the pathophysiology of the most prevalent and lethal diseases in Western countries. We also explore the potential therapeutic impact of new strategies based in the pharmacological modulation of the heterodimeric nuclear receptors.
Cortés
Víctor
V
Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Quezada
Nicolás
N
Rigotti
Attilio
A
Maiz
Alberto
A
D050260:Carbohydrate Metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D050171:Dyslipidemias / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D050356:Lipid Metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism* / Q000627:therapeutic use; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D014158:Transcription, Genetic
D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid