Christina-Maria Flessa1,2, Ioannis Kyrou2,3,4, Narjes Nasiri-Ansari1, Gregory Kaltsas5, Athanasios G Papavassiliou1, Eva Kassi6,7, Harpal S Randeva8,9. 1. Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece. 2. Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, CV2 2DX, UK. 3. Aston Medical Research Institute, Aston Medical School, College of Health and Life Sciences, Aston University, B4 7ET, Birmingham, UK. 4. Division of Translational and Experimental Medicine, Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK. 5. Endocrine Unit, 1st Department of Propaedeutic and Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, 11527, Athens, Greece. 6. Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece. ekassi@med.uoa.gr. 7. Endocrine Unit, 1st Department of Propaedeutic and Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, 11527, Athens, Greece. ekassi@med.uoa.gr. 8. Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, CV2 2DX, UK. harpal.randeva@uhcw.nhs.uk. 9. Division of Translational and Experimental Medicine, Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK. harpal.randeva@uhcw.nhs.uk.
Abstract
PURPOSE OF REVIEW: Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease with rising prevalence worldwide. Herein, we provide a comprehensive overview of the current knowledge supporting the role of ER stress and autophagy processes in NAFLD pathogenesis and progression. We also highlight the interrelation between these two pathways and the impact of ER stress and autophagy modulators on NAFLD treatment. RECENT FINDINGS: The pathophysiological mechanisms involved in NAFLD progression are currently under investigation. The endoplasmic reticulum (ER) stress and the concomitant unfolded protein response (UPR) seem to contribute to its pathogenesis mainly due to high ER content in the liver which exerts significant metabolic functions and can be dysregulated. Furthermore, disruption of autophagy processes has also been identified in NAFLD. The crucial role of these two pathways in NAFLD is underlined by the fact that they have recently emerged as promising targets of therapeutic interventions. There is a greater need for finding the natural/chemical compounds and drugs which can modulate the ER stress pathway and autophagy for the treatment of NAFLD. Clarifying the inter-relation between these two pathways and their interaction with inflammatory and apoptotic mechanisms will allow the development of additional therapeutic options which can better target and reprogram the underlying pathophysiological pathways, aiming to attenuate NAFLD progression.
PURPOSE OF REVIEW: Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease with rising prevalence worldwide. Herein, we provide a comprehensive overview of the current knowledge supporting the role of ER stress and autophagy processes in NAFLD pathogenesis and progression. We also highlight the interrelation between these two pathways and the impact of ER stress and autophagy modulators on NAFLD treatment. RECENT FINDINGS: The pathophysiological mechanisms involved in NAFLD progression are currently under investigation. The endoplasmic reticulum (ER) stress and the concomitant unfolded protein response (UPR) seem to contribute to its pathogenesis mainly due to high ER content in the liver which exerts significant metabolic functions and can be dysregulated. Furthermore, disruption of autophagy processes has also been identified in NAFLD. The crucial role of these two pathways in NAFLD is underlined by the fact that they have recently emerged as promising targets of therapeutic interventions. There is a greater need for finding the natural/chemical compounds and drugs which can modulate the ER stress pathway and autophagy for the treatment of NAFLD. Clarifying the inter-relation between these two pathways and their interaction with inflammatory and apoptotic mechanisms will allow the development of additional therapeutic options which can better target and reprogram the underlying pathophysiological pathways, aiming to attenuate NAFLD progression.
Authors: Suneng Fu; Ling Yang; Ping Li; Oliver Hofmann; Lee Dicker; Winston Hide; Xihong Lin; Steven M Watkins; Alexander R Ivanov; Gökhan S Hotamisligil Journal: Nature Date: 2011-05-01 Impact factor: 49.962