title: Endoplasmic reticulum proteostasis in hepatic steatosis.
abstract: Hepatic steatosis, the first step in the progression of nonalcoholic fatty liver disease, is characterized by triglyceride accumulation in hepatocytes and is highly prevalent in people with obesity. Although initially asymptomatic, hepatic steatosis is an important risk factor for the development of hepatic insulin resistance and type 2 diabetes mellitus and can also progress to more severe pathologies such as nonalcoholic steatohepatitis, liver fibrosis and cirrhosis; hepatic steatosis has, therefore, received considerable research interest in the past 20 years. The lipid accumulation that defines hepatic steatosis disturbs the function of the endoplasmic reticulum (ER) in hepatocytes, thereby generating chronic ER stress that interferes with normal cellular function. Although ubiquitous stress response mechanisms (namely, ER-associated degradation, unfolded protein response and autophagy) are the main processes for restoring cellular proteostasis, these mechanisms are unable to alleviate ER stress in the context of the fatty liver. Furthermore, ER stress and ER stress responses can promote lipid accumulation in hepatocytes in a counter-productive manner and could, therefore, be the origin of a vicious pathological cycle.
authors: Institut National de la Santé et de la Recherche Médicale, UMRS 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, UMRS 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'école de médecine, F-75006, Paris, France.|University of Medicine and Pharmacy Iuliu Hat¸ieganu, Faculty of Pharmacy, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania.
authors: Andrei
authors: A
authors: Baiceanu
authors: Institut National de la Santé et de la Recherche Médicale, UMRS 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, UMRS 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'école de médecine, F-75006, Paris, France.
authors: Pierre
authors: P
authors: Mesdom
authors: Institut National de la Santé et de la Recherche Médicale, UMRS 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, UMRS 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'école de médecine, F-75006, Paris, France.
authors: Marie
authors: M
authors: Lagouge
authors: Institut National de la Santé et de la Recherche Médicale, UMRS 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, UMRS 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, UMRS 1138, Centre de Recherche des Cordeliers, 15 rue de l'école de médecine, F-75006, Paris, France.
authors: Fabienne
authors: F
authors: Foufelle
mesh_terms: D001343:Autophagy; D003924:Diabetes Mellitus, Type 2; D004721:Endoplasmic Reticulum / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D060746:Endoplasmic Reticulum-Associated Degradation; D005234:Fatty Liver / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D009765:Obesity; D015388:Organelles / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*; D056811:Unfolded Protein Response
chemical_list: D011506:Proteins; D014280:Triglycerides