Oxidative stress, cardiolipin and mitochondrial dysfunction in nonalcoholic fatty liver disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is today considered the most common form of chronic liver disease, affecting a high proportion of the population worldwide. NAFLD encompasses a large spectrum of liver damage, ranging from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. Obesity, hyperglycemia, type 2 diabetes and hypertriglyceridemia are the most important risk factors. The pathogenesis of NAFLD and its progression to fibrosis and chronic liver disease is still unknown. Accumulating evidence indicates that mitochondrial dysfunction plays a key role in the physiopathology of NAFLD, although the mechanisms underlying this dysfunction are still unclear. Oxidative stress is considered an important factor in producing lethal hepatocyte injury associated with NAFLD. Mitochondrial respiratory chain is the main subcellular source of reactive oxygen species (ROS), which may damage mitochondrial proteins, lipids and mitochondrial DNA. Cardiolipin, a phospholipid located at the level of the inner mitochondrial membrane, plays an important role in several reactions and processes involved in mitochondrial bioenergetics as well as in mitochondrial dependent steps of apoptosis. This phospholipid is particularly susceptible to ROS attack. Cardiolipin peroxidation has been associated with mitochondrial dysfunction in multiple tissues in several physiopathological conditions, including NAFLD. In this review, we focus on the potential roles played by oxidative stress and cardiolipin alterations in mitochondrial dysfunction associated with NAFLD.

Paeoniflorin Protects against Nonalcoholic Fatty Liver Disease Induced by a High-Fat Diet in Mice

“…Any reasons making the fat metabolism disorder could lead to liver fat deposition. 13) Fatty liver is not an independent disease. It is a common pathological phenomenon that a variety of diseases induce the excessive fat to deposite in hepatocyte.…”

Does Simple Steatosis Affect Liver Regeneration after Partial Hepatectomy in Rats?

“…Accumulating evidence indi- 36 cates that mitochondrial dysfunction participates as a key player in the pathophysiology of NAFLD (15). Besides ultrastructural changes (16) and depletion of mitochondrial DNA (17,18), mitochondrial dysfunction includes altered activities of respiratory complexes and decreased capacity for ATP synthesis (19,20).…”

Oxidative stress and hepatocarcinogenesis

“…Oxidative stress is a crucial factor in the initiation and progression of HCC under various pathological conditions [48] . Oxidative stress can be induced by ROS produced in the mitochondria in non-alcoholic fatty liver disease, which damages hepatocytes, promotes pathologic polyploidization, triggers inflammation, and contributes to insulin resistance [49][50][51][52][53] . Additionally, oxidative stress is also involved in migration, invasion, and metastasis of HCC [54][55][56] .…”