Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. It is characterized by a wide spectrum of hepatic changes, which may progress to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is considered a hepatic manifestation of metabolic syndrome; however, mechanisms underlying the onset and progression of NAFLD are still unclear. Resident and recruited macrophages are key players in the homeostatic function of the liver and in the progression of NAFLD to NASH. Progress has been made in understanding the molecular mechanisms underlying the polarized activation of macrophages. New NAFLD therapies will likely involve modification of macrophage polarization by restraining M1 activation or driving M2 activation. Carotenoids are potent antioxidants and anti-inflammatory micronutrients that have been used to prevent and treat NAFLD. In addition to their antioxidative action, carotenoids can regulate macrophage polarization and thereby halt the progression of NASH. In this review, we summarize the molecular mechanisms of macrophage polarization and the function of liver macrophages/Kupffer cells in NAFLD. From our review, we propose that dietary carotenoids, such as β-cryptoxanthin and astaxanthin, be used to prevent or treat NAFLD through the regulation of macrophage polarization and liver homeostasis.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent
Non-alcoholic steatohepatitis (NASH) is a more severe form of NAFLD that is broadly defined by the presence of steatosis with inflammation and progressive fibrosis [2], leading to cirrhosis and hepatocellular carcinoma (HCC) [3,4,5]
We found that we found that a diet high in fat, cholesterol, and cholate led to the development of pathophysiological a diet high in fat, cholesterol, and cholate led to the development of pathophysiological NASH
Summary
Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent. It is a common cause of chronic liver disease and a major indicator of metabolic syndrome [1]. We found that insulin resistance promoted the progression of NASH from simple fatty liver [7]. Addition of trans fats or high levels of fat to a fructose diet promoted glucose and insulin glucose and insulin insensitivity and fatty liver formation without fibrosis [12]. Hepatic macrophages, which consist of resident KCs and recruited bone marrow-derived macrophages, are the major cells that produce inflammatory mediators, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, causing systemic insulin resistance and, NASH [19]. Cross-sectional and prospective studies have shown that physical activity decreases intrahepatic lipid levels [29] Both aerobic and resistance exercises have been shown to improve liver function, independently of weight loss [30,31]. Pathology is frequently associated with dynamic changes in macrophage activation, with classically-activated M1 cells implicated in initiating and sustaining inflammation, and M2 or M2-like cells associated with decreasing chronic inflammation [47]
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