title: Lipotoxicity in the liver.
abstract: Obesity due to excessive food intake and the lack of physical activity is becoming one of the most serious public health problems of the 21(st) century. With the increasing prevalence of obesity, non-alcoholic fatty liver disease is also emerging as a pandemic. While previously this pathophysiological condition was mainly attributed to triglyceride accumulation in hepatocytes, recent data show that the development of oxidative stress, lipid peroxidation, cell death, inflammation and fibrosis are mostly due to accumulation of fatty acids, and the altered composition of membrane phospholipids. In fact, triglyceride accumulation might play a protective role, and the higher toxicity of saturated or trans fatty acids seems to be the consequence of a blockade in triglyceride synthesis. Increased membrane saturation can profoundly disturb cellular homeostasis by impairing the function of membrane receptors, channels and transporters. However, it also induces endoplasmic reticulum stress via novel sensing mechanisms of the organelle's stress receptors. The triggered signaling pathways in turn largely contribute to the development of insulin resistance and apoptosis. These findings have substantiated the lipotoxic liver injury hypothesis for the pathomechanism of hepatosteatosis. This minireview focuses on the metabolic and redox aspects of lipotoxicity and lipoapoptosis, with special regards on the involvement of endoplasmic reticulum stress responses.
authors.affiliation: Veronika Zámbó, Laura Simon-Szabó, Péter Szelényi, Éva Kereszturi, Gábor Bánhegyi, Miklós Csala, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, H-1444 Budapest, Hungary.
authors.forename: Veronika
authors.initials: V
authors.lastname: Zámbó
authors.forename: Laura
authors.initials: L
authors.lastname: Simon-Szabó
authors.forename: Péter
authors.initials: P
authors.lastname: Szelényi
authors.forename: Eva
authors.initials: E
authors.lastname: Kereszturi
authors.forename: Gábor
authors.initials: G
authors.lastname: Bánhegyi
authors.forename: Miklós
authors.initials: M
authors.lastname: Csala
keywords: Endoplasmic reticulum stress; Lipoapoptosis; Lipotoxicity; Saturated fatty acid; Steatosis