Non-alcoholic fatty liver disease (NAFLD) has become one of the most common metabolic liver diseases worldwide with an estimated prevalence ranging from 25% to 45%. NAFLD is defined as accumulation of lipids, mainly triglycerides, in more than 5% of hepatocytes with no evidence of excessive alcohol consumption or other secondary causes. The spectrum of NAFLD ranges from simple steatosis, a non-progressive disease entity with absence of hepatic inflammation and fibrosis, to non-alcoholic steatohepatitis (NASH), the most progressive and severe condition that can develop into cirrhosis, hepatocellular carcinoma and liver-related mortality.
Despite the burden of NAFLD on global public health, there is yet no FDA approved medication for treating NAFLD, especially NASH or advanced fibrosis. Therefore, elucidating tangled mechanisms of NASH can lead to identify promising therapeutic targets for treating NASH. Furthermore, diagnosing NASH is currently inaccurate without conducting liver biopsy.
To delineate NAFLD, numerous animal models have been generated and reported. Increased consumption of fructose as well as high fat diet has been well documented to contribute to develop NAFLD, dyslipidemia, and insulin resistance. However, the detailed mechanisms of increased high carbo/high fat nutrient consumption to dysregulate hepatic gluconeogenesis and lipogenesis still remain unclear. Numerous transcriptional factors, including ChREBP, SREBP1c, and nuclear receptor PPAR gamma that regulate gluconeogenesis and lipogenesis are affected by fructose-derived precursors or nutrients to control the expression of their target genes.
Besides of nutrient challenge, various genetic models have also been reported to develop NAFLD. For example, as nuclear hormone receptor PPAR alpha regulates fatty acid oxidation, PPAR alpha-null mice can develop hepatic steatosis under fasting condition within 24 hours. In consistent with PPAR alpha-null mice, histone deacetylase 3 (HDAC3)-deficient animal has been shown to develop hepatic steatosis as HDAC3 represses genes involved in hepatic lipid synthesis and sequestration.
Multiple molecular pathways disrupted in obesity and NAFLD are under control of nutrients and key metabolic genes, and the mechanisms involved in the accumulation of triglyceride in the liver are not completely understood. A greater knowledge of the etiopathogenic mechanisms of NAFLD is fundamental to establish diagnostic method, to find novel biomarkers and finally to develop further effective therapeutic strategies.
In this Research Topic, we will welcome articles dissecting novel mechanisms and demonstrating diagnostic or therapeutic approaches in NAFLD, including NASH and advanced fibrosis.
Non-alcoholic fatty liver disease (NAFLD) has become one of the most common metabolic liver diseases worldwide with an estimated prevalence ranging from 25% to 45%. NAFLD is defined as accumulation of lipids, mainly triglycerides, in more than 5% of hepatocytes with no evidence of excessive alcohol consumption or other secondary causes. The spectrum of NAFLD ranges from simple steatosis, a non-progressive disease entity with absence of hepatic inflammation and fibrosis, to non-alcoholic steatohepatitis (NASH), the most progressive and severe condition that can develop into cirrhosis, hepatocellular carcinoma and liver-related mortality.
Despite the burden of NAFLD on global public health, there is yet no FDA approved medication for treating NAFLD, especially NASH or advanced fibrosis. Therefore, elucidating tangled mechanisms of NASH can lead to identify promising therapeutic targets for treating NASH. Furthermore, diagnosing NASH is currently inaccurate without conducting liver biopsy.
To delineate NAFLD, numerous animal models have been generated and reported. Increased consumption of fructose as well as high fat diet has been well documented to contribute to develop NAFLD, dyslipidemia, and insulin resistance. However, the detailed mechanisms of increased high carbo/high fat nutrient consumption to dysregulate hepatic gluconeogenesis and lipogenesis still remain unclear. Numerous transcriptional factors, including ChREBP, SREBP1c, and nuclear receptor PPAR gamma that regulate gluconeogenesis and lipogenesis are affected by fructose-derived precursors or nutrients to control the expression of their target genes.
Besides of nutrient challenge, various genetic models have also been reported to develop NAFLD. For example, as nuclear hormone receptor PPAR alpha regulates fatty acid oxidation, PPAR alpha-null mice can develop hepatic steatosis under fasting condition within 24 hours. In consistent with PPAR alpha-null mice, histone deacetylase 3 (HDAC3)-deficient animal has been shown to develop hepatic steatosis as HDAC3 represses genes involved in hepatic lipid synthesis and sequestration.
Multiple molecular pathways disrupted in obesity and NAFLD are under control of nutrients and key metabolic genes, and the mechanisms involved in the accumulation of triglyceride in the liver are not completely understood. A greater knowledge of the etiopathogenic mechanisms of NAFLD is fundamental to establish diagnostic method, to find novel biomarkers and finally to develop further effective therapeutic strategies.
In this Research Topic, we will welcome articles dissecting novel mechanisms and demonstrating diagnostic or therapeutic approaches in NAFLD, including NASH and advanced fibrosis.
