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Losartan Prevents Hepatic Steatosis and Macrophage Polarization by Inhibiting HIF-1α in a Murine Model of NAFLD.
Wang, Cheng-Hui; Liu, Hsuan-Miao; Chang, Zi-Yu; Huang, Tse-Hung; Lee, Tzung-Yan.
Afiliación
  • Wang CH; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan City 333, Taiwan.
  • Liu HM; Graduate Institute of Traditional Chinese Medicine, School of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan City 333, Taiwan.
  • Chang ZY; Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung City 204, Taiwan.
  • Huang TH; Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
  • Lee TY; Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung City 204, Taiwan.
Int J Mol Sci ; 22(15)2021 Jul 22.
Article en En | MEDLINE | ID: mdl-34360607
Hypoxia and hepatosteatosis microenvironments are fundamental traits of nonalcoholic fatty liver disease (NAFLD). Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that controls the cellular response to hypoxia and is activated in hepatocytes of patients with NAFLD, whereas the route and regulation of lipid droplets (LDs) and macrophage polarization related to systemic inflammation in NAFLD is unknown. Losartan is an angiotensin II receptor antagonist, that approved portal hypertension and related HIF-1α pathways in hepatic injury models. Here, we show that losartan in a murine model of NAFLD significantly decreased hepatic de novo lipogenesis (DNL) as well as suppressed lipid droplets (LDs), LD-associated proteins, perilipins (PLINs), and cell-death-inducing DNA-fragmentation-factor (DFF45)-like effector (CIDE) family in liver and epididymal white adipose tissues (EWAT) of ob/ob mice. Obesity-mediated macrophage M1 activation was also required for HIF-1α expression in the liver and EWAT of ob/ob mice. Administration of losartan significantly diminishes obesity-enhanced macrophage M1 activation and suppresses hepatosteatosis. Moreover, HIF-1α-mediated mitochondrial dysfunction was reversed in ob/ob mice treated with losartan. Together, the regulation of HIF-1α controls LDs protein expression and macrophage polarization, which highlights a potential target for losartan in NAFLD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Losartán / Subunidad alfa del Factor 1 Inducible por Hipoxia / Hígado Graso / Enfermedad del Hígado Graso no Alcohólico / Activación de Macrófagos Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Losartán / Subunidad alfa del Factor 1 Inducible por Hipoxia / Hígado Graso / Enfermedad del Hígado Graso no Alcohólico / Activación de Macrófagos Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Suiza