Docosahexaenoic acid and its role in G-protein-coupled receptor 120 activation in children affected by nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is one of the most important causes of chronic liver disease in children and adults. Recently, therapeutic supplementation with docosahexaenoic acid (DHA) showed an anti-inflammatory and insulin-sensitizing effect in children with NAFLD. The anti-inflammatory effects of DHA depend on its ability to alter phospholipid composition of the cell membrane, to disrupt lipid rafts and to hamper the transcriptional activity of nuclear factor-κB that controls the expression of proinflammatory cytokines. These effects of DHA are due to the interaction with the G-protein-coupled receptor 120 (GRP120), a lipid-sensing receptor highly expressed in activated macrophages. In fact, DHA may activate GPR120 expression in macrophages causing anti-inflammatory effects, and insulin-sensitizing and antidiabetic effects in vivo. Recently, it has been shown that GPR120 is also expressed by the Kupffer cells of the liver. A diet low in n-3 polyunsaturated fatty acids, as well as the presence of genetic factors, may induce a reduction in the GRP120 signal and the activation of Kupffer cells and inflammation during NAFLD. Therefore, it is conceivable that DHA/GRP120 may play a key role in slowing the progression of liver damage in patients with NAFLD.