Osteopontina key regulator of liver lipid metabolism

  1. NUÑEZ GARCIA, MAITANE
Dirigida por:
  1. Patricia Aspichueta Celaa Director/a
  2. Olatz Fresnedo Aranguren Director/a

Universidad de defensa: Universidad del País Vasco - Euskal Herriko Unibertsitatea

Fecha de defensa: 25 de abril de 2016

Tribunal:
  1. José Juan García Marín Presidente/a
  2. Begoña Ochoa Olascoaga Secretario/a
  3. Manlio Vinciguerra Vocal
Departamento:
  1. Fisiología

Tipo: Tesis

Teseo: 120741 DIALNET lock_openADDI editor

Resumen

Osteopontin deficiency protects from obesity-related hepatosteatosis and liver fibrosis. Here we have investigated the role of osteopontin as a direct regulator of liver metabolism and whether osteopontin could be a serum-biomarker of liver metabolic dysfunction in non-alcoholic fatty-liver (NAFL) disease patients. We demonstrate that osteopontin regulates the crosstalk between liver cholesterol and phosphatidylcholine metabolism, being the key process the conversion of cholesterol into bile acids, frequently decreased in NAFL. In osteopontin-deficient mice enhanced cholesterogenesis in hepatocytes leads to decreased de novo lipogenesis and in vivo inhibition of cholesterogenesis normalizes liver phosphatidylcholine content. Finally, serum osteopontin levels correlate with liver phosphatidylcholine and cholesterol concentration in non-obese NAFL patients, in whom adipose tissue metabolic deregulation is not evident and conversion of cholesterol into bile acids is decreased. In conclusion, osteopontin is a key regulator of liver lipid metabolism and may be an early serum-biomarker of metabolic deregulation in non-obese NAFL patients.