Impaired adipose tissue function and
insulin resistance remain instrumental in promoting hepatic
lipid accumulation in conditions of
metabolic syndrome. In fact, enhanced
lipid accumulation together with oxidative stress and an abnormal inflammatory response underpin the development and severity of
non-alcoholic fatty liver disease (
NAFLD). There are currently no specific
protective drugs against
NAFLD, and effective interventions involving regular exercise and healthy diets have proved difficult to achieve and maintain. Alternatively, due to its
antioxidant and anti-inflammatory properties, there has been growing interest in understanding the
therapeutic effects of N-acetyl
cysteine (NAC) against metabolic complications, including
NAFLD. Here, reviewed evidence suggests that NAC blocks hepatic
lipid accumulation in preclinical models of
NAFLD. This is in part through the effective regulation of a
fatty acid scavenger molecule (CD36) and transcriptional factors such as
sterol regulatory element-binding protein (
SREBP)-1c/-2 and
peroxisome proliferator-activated receptor gamma (PPARγ). Importantly, NAC appears effective in improving liver function by reducing pro-inflammatory markers such as
interleukin (IL)-6 IL-1β, tumour
necrosis factor alpha (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). This was primarily through the attenuation of lipid peroxidation and enhancements in intracellular response
antioxidants, particularly
glutathione. Very few clinical studies support the beneficial effects of NAC against
NAFLD-related complications, thus well-organized randomized clinical trials are still necessary to confirm its therapeutic potential.