Obesity due to excessive food intake and the lack of physical activity is becoming
one of the most serious public health problems of the 21st 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.
