Emerging molecular targets for the treatment of nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic fat accumulation in the absence of significant ethanol consumption, viral infection, or other specific causes of liver disease. Currently the most common chronic liver disease, affecting 30% of the Western world, NAFLD may progress to cirrhosis and end-stage liver disease and may increase the risk of developing diabetes and cardiovascular disease. Although its pathogenesis is unclear, NAFLD is tightly associated with insulin resistance and the metabolic syndrome. No established treatment exists, and current research is targeting new molecular mechanisms that underlie NAFLD and associated cardiometabolic disorders. This review discusses some of these emerging molecular mechanisms and their therapeutic implications for the treatment of NAFLD: microRNAs, incretin analogs/antagonists, liver-specific thyromimetics, AMP-activated protein kinase activators, and nuclear receptors farnesoid X receptor and pregane X receptor.
Musso
Giovanni
G
Gradenigo Hospital, Turin, Italy. giovanni_musso@yahoo.it
Gambino
Roberto
R
Cassader
Maurizio
M
D055372:AMP-Activated Protein Kinases / Q000187:drug effects / Q000235:genetics; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D005749:Gastric Inhibitory Polypeptide / Q000627:therapeutic use; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D006801:Humans; D054795:Incretins / Q000627:therapeutic use; D035683:MicroRNAs; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000235:genetics*
D005765:Gastrointestinal Agents; D054795:Incretins; D035683:MicroRNAs; D018160:Receptors, Cytoplasmic and Nuclear; D005749:Gastric Inhibitory Polypeptide; D055372:AMP-Activated Protein Kinases