Our study demonstrated that SUA levels are associated with NAFLD in a non obese chinese population.. The NAFLD prevalence increased with increments in SUA level. Besides, there were remarkably elevated risks for NAFLD in individuals with high SUA level in the non-obese Chinese population.
NAFLD is among the most frequent causes of chronic liver disease globally. In a recent study, NAFLD has been shown to be the primary cause of chronic liver disease, as well as cirrhosis . Moreover, NAFLD is an independent predisposing factor of not only hepatocellular carcinoma along with cirrhosis, but also of cardiovascular disease, as well as type 2 diabetes . Studies have shown that the predisposing factors for the progression of include insulin resistance, oxidative stress, as well as systemic inflammation [20, 21].
Previous studies have documented the relationship between elevated levels of SUA and NAFLD in the population. Yanru Chen et al reported that high levels of SUA were associated with NAFLD in women and were remarkably also associated with menstrual status . Fengjiang Wei reported that SUA is positively linked to NAFLD and could be applied as an independent indicator of NAFLD. Another contemporary cross-sectional and longitudinal study established a relationship between SUA and the onset and progress of NAFLD.. In addition, the pathogenic influence of SUA on NAFLD is more remarkable in females as compared to males . Alihan Oral et al documented that the UA level was remarkably and independently linked to hepatocellular steatosis, as well as the NAFLD stage in individuals with biopsy-proven NAFLD .
The pathogenesis of NAFLD has not yet been fully elucidated. The onset and the progress of NAFLD are caused by a combined effect of genetic and environmental factors. The specific mechanism of the positive relationship of SUA with NAFLD is still unclear, and there are several theories at present. Uric acid stimulates inflammation by producing P38 mitogen-activated protein kinase (MAPK), cyclocyte 2 (COX-2), and chemotaxis to monocyte chemotaxis protein 1. Moreover, Uric acid enhances the lipogenesis of fructose by increasing ketohexokinase (KHK) expression, leading to triglyceride accumulation in liver cells. The presence of insulin resistance in NAFLD may increase serum uric acid by decreasing the rate of uric acid clearance in the proximal renal tubules [24, 25]. Hyperuricemia is a component of metabolic syndrome, and elevated levels of SUA can enhance oxidative stress and increased levels of reactive oxygen species. Another possible explanation for the relationship of SUA levels with NAFLD is the presence of pancreatic hyperleptinemia. Some studies have also shown the role of leptin in hyperuricemia. Multiple studies have documented that leptin triggers oxidative stress in endothelial cells, which increases the SUA level . In addition, leptin participation in sodium tube reabsorption could result in an increase in blood SUA level. The NLRP3 inflammatory complex plays an important role in obesity, insulin resistance, abnormal lipid metabolism, and liver cell steatosis . Increased uric acid levels can cause a significant up-regulation of NLRP3 levels in mouse liver cells. When the level of uric acid increases, the expression of aldose reductase in human liver cells is up-regulated, and then glucose is transferred to the polyol pathway, leading to the production, metabolism and fat accumulation of endogenous fructose.
The relationship of SUA level with NAFLD implies that uric acid has a vital role in the occurrence and progress of NAFLD. Uric acid is considered as a natural scavenger of peroxynitrite, as well as peroxynitrite derived free radicals . For a long time, animal experiments and clinical studies have recognized the increase of systemic oxidative stress in NAFLD patients. The increase in SUA may show a compensatory mechanism that counteracts the increase in NAFLD-related oxidative stress. NAFLD has been shown to increase the risk of cardiovascular disease. Simultaneously, uric acid can stimulate the proliferation of vascular smooth muscle, as well as mediate vascular endothelial dysfunction , which could result in vascular inflammation and arterial damage, hence elevating the risk of cardiovascular disease. On this basis, treatment by lowering SUA may have a beneficial effect on reducing cardiovascular disease risk in individuals with NAFLD.
There are several potential limitations to our study that need to be noted. Firstly, dietary factors which might affect SUA levels such asmeat, and fructose intake were not adjusted for the study.,. Secondly, for all the included studies, NAFLD was confirmed by ultrasonography, and there was no histological diagnosis of fatty liver. Although liver ultrasonography is not the gold standard, it is the first-line diagnostic imaging approach for NAFLD. Liver ultrasonography has the characteristics of non-invasiveness and safety. Thirdly, the subjects of this study are mostly residents of Wenzhou, China and the relationship of NAFLD with SUA levels may be different due to different lifestyles and dietary habits in other places. Finally, the association of NAFLD with SUA may be impacted by other unmeasured confounders.