Abstract
The progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) is linked to systemic inflammation. Currently, two of the aspects that need further investigation are diagnosis and treatment of NASH. In this sense, the aim of this study was to assess the relationship between circulating levels of cytokines, hepatic expression of toll-like receptors (TLRs), and degrees of NAFLD, and to investigate whether these levels could serve as noninvasive biomarkers of NASH. The present study assessed plasma levels of cytokines in 29 normal-weight women and 82 women with morbid obesity (MO) (subclassified: normal liver (n = 29), simple steatosis (n = 32), and NASH (n = 21)). We used enzyme-linked immunosorbent assays (ELISAs) to quantify cytokine and TLR4 levels and RTqPCR to assess TLRs hepatic expression. IL-1β, IL-8, IL-10, TNF-α, tPAI-1, and MCP-1 levels were increased, and adiponectin levels were decreased in women with MO. IL-8 was significantly higher in MO with NASH than in NL. To sum up, high levels of IL-8 were associated with the diagnosis of NASH in a cohort of women with morbid obesity. Moreover, a positive correlation between TLR2 hepatic expression and IL-8 circulating levels was found.
Highlights
Nonalcoholic fatty liver disease (NAFLD) comprises a wide spectrum of liver cell injuries that range from simple steatosis (SS) to nonalcoholic steatohepatitis (NASH) [1,2]
On the one hand, circulating levels of some proinflammatory cytokines seem to be directly related to NAFLD progression, such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-8, monocyte chemoattractant protein (MCP)-1, IL-6, IL-13, plasminogen activator inhibitor (PAI)-1, and IL-17 [21,22,23,24,25,26]
Biochemical analyses indicated that women with morbid obesity (MO) had significantly higher levels of fasting glucose (p < 0.001), insulin (p < 0.001), glycosylated hemoglobin (HbA1c) (p = 0.032), homeostatic model assessment method insulin resistance (HOMA)2-Insulin resistance (IR) (p < 0.001), and triglycerides (TGL) (p < 0.001) than NW women
Summary
Nonalcoholic fatty liver disease (NAFLD) comprises a wide spectrum of liver cell injuries that range from simple steatosis (SS) to nonalcoholic steatohepatitis (NASH) [1,2]. The result is an obesity-associated low-grade systemic inflammation that is characterized by the recruitment of macrophages and increased levels of proinflammatory cytokines and chemokines, as well as the activation of several kinases and transcription factors that regulate inflammation and insulin sensitivity in adipocytes and hepatocytes [9,10]. Adipocytokines are mediators in many of these processes, and adipocytokine deregulation leads to an activation of the immune system, a shift to the proinflammatory M1-phenotype of macrophages, and activation of hepatic stellate cells [17,19]. These changes contribute to a vicious cycle that perpetuates the inflammatory response and hepatocyte damage [20]. The extensive inflammation associated with cytokine/chemokine release leads to the accumulation of extracellular matrix, the development of fibrosis, and further deterioration of liver function [30] (Figure 1)
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