Role of Ca(2+) channels in non-alcoholic fatty liver disease and their implications for therapeutic strategies (Review)

Non-alcoholic fatty liver disease (NAFLD) is a clinically progressive illness that can advance from simple fatty liver to non-alcoholic hepatitis and liver fibrosis. Cirrhosis and hepatocellular carcinoma are two of the most common diseases caused by NAFLD. As there are no early disease biomarkers and no US Food and Drug Administration-approved medications, treatment for NAFLD is still focused on altering lifestyle and dietary habits, which makes it difficult to treat effectively. As a result, a novel treatment is urgently needed to prevent NAFLD progression. Calcium (Ca(2+)) channels regulate intracellular Ca(2+) homeostasis via the mediation of Ca(2+) flow. Previous studies have reported that Ca(2+) channel expression varies throughout the development and progression of NAFLD, which results in the dysregulation of intracellular Ca(2+) homeostasis, endoplasmic reticulum stress, mitochondrial dysfunction and autophagy suppression, all of which contribute to NAFLD progression. Several types of Ca(2+) channels (including two-pore segment channel 2, transient receptor potential, inositol triphosphate receptor, voltage-dependent anion channel 1, store-operated Ca(2+) entry, purinergic receptor X7 and potassium Ca(2+)-activated channel subfamily N member 4) have been identified as potential targets for preventing NAFLD development and controlling intracellular Ca(2+) homeostasis. To achieve this, these channels can be blocked or activated, which exerts anti-steatotic, anti-inflammatory, anti-fibrotic and other effects, which ultimately prevents the development of NAFLD. In the present review NAFLD therapeutics and the treatments that target Ca(2+) channels that are currently being developed were examined.