Abstract
Industrialized society-caused dysregular human behaviors and activities such as overworking, excessive dietary intake, and sleep deprivation lead to perturbations in the metabolism and the development of metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease worldwide, affects around 30% and 25% of people in Western and Asian countries, respectively, which leads to numerous medical costs annually. Insulin resistance is the major hallmark of NAFLD and is crucial in the pathogenesis and for the progression from NAFLD to non-alcoholic steatohepatitis (NASH). Excessive dietary intake of saturated fats and carbohydrate-enriched foods contributes to both insulin resistance and NAFLD. Once NAFLD is established, insulin resistance can promote the progression to the more severe state of liver endangerment like NASH. Here, we review current and potential studies for understanding the complexity between insulin-regulated glycolytic and lipogenic homeostasis and the underlying causes of NAFLD. We discuss how disruption of the insulin signal is associated with various metabolic disorders of glucoses and lipids that constitute both the metabolic syndrome and NAFLD.
Highlights
Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide because of its complex pathogenesis and difficulty in diagnosis
The first hit for NAFLD development was the generation of hepatic steatosis through aberrant accumulation of TGs in hepatocytes, called steatosis which is the hallmark feature in non-alcoholic fatty liver (NAFL)
Especially a high-fat diet, inactive lifestyle, and genetic variants have been shown to be involved in the progression of NAFLD, insulin resistance (IR) is considered to play a key role in the formation of non-alcoholic steatohepatitis (NASH), which lead to hepatic de novo lipogenesis, reduction of lipolysis of adipose tissue, and consequent elevation of free fatty acid (FFA) in the liver [21]
Summary
Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide because of its complex pathogenesis and difficulty in diagnosis. NASH usually displays lobular inflammation and hepatocyte ballooning histologically with injured hepatocyte in a background of steatosis, which is associated with faster fibrosis progression than NAFLD [5,6,7]. Particular stains such as cytoplasmic keratin (KRT) 8/18 immunohistochemistry may detect ballooned hepatocytes. A recent study by Golob-Schwarzl et al [8] found that a high KRT8/18 ratio caused the change in hepatic lipid profile resulting in ballooning with a Mallory–Denk body (MDB) formation Numerous risk factors, such as metabolic derangement, obesity, and insulin resistance (IR) lead to liver accumulation of triglycerides and free fatty acids and growing of NAFLD [9].
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