The global epidemic of obesity and insulin-resistance during the last decades has been responsible for a dramatic increase in the prevalence of non-alcoholic fatty liver disease (NAFLD). To find possible treatments for NAFLD and associated conditions it is crucial to understand the roles of the different enzymes involved.
By Verónica Miksztowicz
Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent disorder worldwide, and is closely related to insulin-resistance and cardiovascular disease. NAFLD itself is characterized by an accumulation of fat in the liver in the absence of alcohol consumption. The condition can lead to different liver alterations, with 10 to 20% of patients developing fibrosis and cirrhosis.
What is liver fibrosis?
Fibrosis is defined by an increased deposition of extracellular matrix (ECM) components in a tissue or organ. The extracellular matrix can be thought of as a mesh of non-cellular macromolecules, such as collagen fibres and proteins, which serve a variety of different functions like providing structural support and controlling intercellular communication. The excessive accumulation of ECM components in the liver results in scarring and thickening of the tissue and can ultimately lead to liver cirrhosis.
The stages of liver disease © NIDDK
The role of enzymes: a controversial subject
Matrix metalloproteinases (MMPs) constitute a family of enzymes that are involved in the degradation of extracellular matrix proteins. The development of liver fibrosis is characterized by an altered composition of the extracellular matrix, associated with modifications in the behaviour of MMP enzymes. However, the exact mechanisms are still the subject of a controversial debate.
In a recent review, published in Hormone Molecular Biology and Clinical Investigation, Argentine researchers argue that an improved knowledge about the behaviour of MMP enzymes in liver fibrosis could trigger the design of new specific drugs to prevent the progression of non-alcoholic fatty liver disease. The researchers furthermore speculate that adipokines – proteins secreted by adipose tissue – might influence the behaviour of MMP enzymes and could thus be partly responsible for liver damage during insulin resistance and obesity.
In light of the continuing rise of obesity and associated diseases worldwide, further research is now needed to investigate matrix metalloproteinases as a potential therapeutic target for the treatment of liver disease.
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