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Micronutrient Antioxidants and Nonalcoholic Fatty Liver Disease

View Article: PubMed Central - PubMed

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is one of the most important chronic liver diseases worldwide and has garnered increasing attention in recent decades. NAFLD is characterized by a wide range of liver changes, from simple steatosis to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. The blurred pathogenesis of NAFLD is very complicated and involves lipid accumulation, insulin resistance, inflammation, and fibrogenesis. NAFLD is closely associated with complications such as obesity, diabetes, steatohepatitis, and liver fibrosis. During the progression of NAFLD, reactive oxygen species (ROS) are activated and induce oxidative stress. Recent attempts at establishing effective NAFLD therapy have identified potential micronutrient antioxidants that may reduce the accumulation of ROS and finally ameliorate the disease. In this review, we present the molecular mechanisms involved in the pathogenesis of NAFLD and introduce some dietary antioxidants that may be used to prevent or cure NAFLD, such as vitamin D, E, and astaxanthin.

No MeSH data available.


Related in: MedlinePlus

Hypothetic mechanism of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) progression. Excessive intake of excess calories and fat results in accumulation of triglycerides, total cholesterol, and free fatty acids, inducing hepatic steatosis. The overload of liver lipids enhances lipid peroxidation, which induces the production of reactive oxygen species and steatohepatitis. Hepatic inflammation activates the mitogen-activated protein kinase pathway and nuclear factor-κB, resulting in insulin resistance. Insulin resistance also promotes de novo lipogenesis, forcing the healthy liver to develop NASH. The inflammation also recruits Kupffer cells and polarizes M1 macrophages, activating hepatic stellate cells and finally leading to liver fibrosis. TG, triglycerides; TC, total cholesterol; FFA, free fatty acids; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor-κB.
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ijms-17-01379-f001: Hypothetic mechanism of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) progression. Excessive intake of excess calories and fat results in accumulation of triglycerides, total cholesterol, and free fatty acids, inducing hepatic steatosis. The overload of liver lipids enhances lipid peroxidation, which induces the production of reactive oxygen species and steatohepatitis. Hepatic inflammation activates the mitogen-activated protein kinase pathway and nuclear factor-κB, resulting in insulin resistance. Insulin resistance also promotes de novo lipogenesis, forcing the healthy liver to develop NASH. The inflammation also recruits Kupffer cells and polarizes M1 macrophages, activating hepatic stellate cells and finally leading to liver fibrosis. TG, triglycerides; TC, total cholesterol; FFA, free fatty acids; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor-κB.

Mentions: The mainstream concept of NAFLD is the “multiple parallel hits” hypothesis, which developed from the two-hit theory proposed by Day et al. [24] in 1998. The two-hit theory states that a high-fat diet or diabetes-induced steatosis (the first hit) will make the liver more sensitive to other risk factors related to oxidative stress and induce severe lipid peroxidation (the second hit). The multiple parallel hits theory states that NAFLD is a more comprehensive effect of diverse factors, such as endoplasmic reticulum stress, chemokines and cytokines, and innate immunity, than a simple effect of one or two factors, which may explain why NAFLD is also observed in lean people [25] (Figure 1).


Micronutrient Antioxidants and Nonalcoholic Fatty Liver Disease
Hypothetic mechanism of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) progression. Excessive intake of excess calories and fat results in accumulation of triglycerides, total cholesterol, and free fatty acids, inducing hepatic steatosis. The overload of liver lipids enhances lipid peroxidation, which induces the production of reactive oxygen species and steatohepatitis. Hepatic inflammation activates the mitogen-activated protein kinase pathway and nuclear factor-κB, resulting in insulin resistance. Insulin resistance also promotes de novo lipogenesis, forcing the healthy liver to develop NASH. The inflammation also recruits Kupffer cells and polarizes M1 macrophages, activating hepatic stellate cells and finally leading to liver fibrosis. TG, triglycerides; TC, total cholesterol; FFA, free fatty acids; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor-κB.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037659&req=5

ijms-17-01379-f001: Hypothetic mechanism of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) progression. Excessive intake of excess calories and fat results in accumulation of triglycerides, total cholesterol, and free fatty acids, inducing hepatic steatosis. The overload of liver lipids enhances lipid peroxidation, which induces the production of reactive oxygen species and steatohepatitis. Hepatic inflammation activates the mitogen-activated protein kinase pathway and nuclear factor-κB, resulting in insulin resistance. Insulin resistance also promotes de novo lipogenesis, forcing the healthy liver to develop NASH. The inflammation also recruits Kupffer cells and polarizes M1 macrophages, activating hepatic stellate cells and finally leading to liver fibrosis. TG, triglycerides; TC, total cholesterol; FFA, free fatty acids; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor-κB.
Mentions: The mainstream concept of NAFLD is the “multiple parallel hits” hypothesis, which developed from the two-hit theory proposed by Day et al. [24] in 1998. The two-hit theory states that a high-fat diet or diabetes-induced steatosis (the first hit) will make the liver more sensitive to other risk factors related to oxidative stress and induce severe lipid peroxidation (the second hit). The multiple parallel hits theory states that NAFLD is a more comprehensive effect of diverse factors, such as endoplasmic reticulum stress, chemokines and cytokines, and innate immunity, than a simple effect of one or two factors, which may explain why NAFLD is also observed in lean people [25] (Figure 1).

View Article: PubMed Central - PubMed

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is one of the most important chronic liver diseases worldwide and has garnered increasing attention in recent decades. NAFLD is characterized by a wide range of liver changes, from simple steatosis to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. The blurred pathogenesis of NAFLD is very complicated and involves lipid accumulation, insulin resistance, inflammation, and fibrogenesis. NAFLD is closely associated with complications such as obesity, diabetes, steatohepatitis, and liver fibrosis. During the progression of NAFLD, reactive oxygen species (ROS) are activated and induce oxidative stress. Recent attempts at establishing effective NAFLD therapy have identified potential micronutrient antioxidants that may reduce the accumulation of ROS and finally ameliorate the disease. In this review, we present the molecular mechanisms involved in the pathogenesis of NAFLD and introduce some dietary antioxidants that may be used to prevent or cure NAFLD, such as vitamin D, E, and astaxanthin.

No MeSH data available.


Related in: MedlinePlus