The role of folate in non-alcoholic fatty liver disease
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of chronic liver diseases that are characterized by steatosis (hepatic lipid accumulation), inflammation, fibrosis, and liver injury. Chronic consumption of high-fat diets is a major cause of obesity and NAFLD. Because NAFLD is a multifaceted disorder with many underlying metabolic abnormalities, currently, there is no pharmacological agent that is therapeutically approved for the treatment of NAFLD. Folate is a water-soluble B vitamin that has been demonstrated to have antioxidant functions and lipid-lowering effects. The general objective of my research was to investigate the role of folate in the context of high-fat diet-induced NAFLD. A low level of folate in the circulation is often observed in patients with obesity. A low level of endogenous folates in rodents perturbs folate-dependent one-carbon metabolism, and may be associated with development of metabolic diseases such as NAFLD. The first part of my research focused on identifying the underlying mechanisms that are responsible for regulating folate status during high-fat diet feeding. Our results have shown that high-fat diet feeding reduces folate levels in the liver and serum by attenuating expression of hepatic folate transporters in mice. Such effect is mediated through inhibition of nuclear respiratory factor-1 (NRF-1), an important transcriptional regulator of folate transporters. Hepatic lipid and glucose metabolism is frequently perturbed in patients…
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