[Role of PPARs in the pathophysiology of nonalcoholoic fatty liver disease].
Pathogenic role of intrahepatic lipid accumulation in insulin resistance and metabolic syndrome has been well documented. Liver steatosis constitutes a risk factor for nonalcoholic steatohepatitis (NASH), one of the leading causes of obesity-related morbidity and mortality. Although pathophysiology of steatosis is multifactorial, a line of evidence from rodent studies suggests that PPARalpha and PPARgamma are involved. PPARalpha is highly expressed in liver and its activation by agonists leads to augmented fatty acid oxidation and protects against steatosis. PPARgamma, which is transcriptionally up-regulated in steatosis, activates lipogenic enzymes and exacerbates steatosis. However, recent human studies have suggested that PPARgamma agonists improve NASH possibly by its primary insulin-sensitizing effect on adipocytes. PPARs modulation is becoming a rational and effective therapeutic approach for the treatment of nonalcoholic fatty liver disease.
Tanaka
Tomohiro
T
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine.
Masuzaki
Hiroaki
H
Nakao
Kazuwa
K
D005234:Fatty Liver / Q000209:etiology*; D050356:Lipid Metabolism; D024821:Metabolic Syndrome / Q000209:etiology; D047493:PPAR alpha / Q000502:physiology*; D047495:PPAR gamma / Q000502:physiology*
D047493:PPAR alpha; D047495:PPAR gamma