## 4 Discussion
In addition, factors such as lipopolysaccharide (LPS) and inflammatory cytokines such as TNF-\(\alpha\) increase in patients with NAFLD, leading to decreased AMPK activity [38; 39]. Our results demonstrated that FGK suppressed the expression of these inflammatory mediators, further contributing to the restoration of AMPK activity and energy homeostasis. Therefore, regulation of inflammatory factors in the context of NAFLD is a key area for future research to understand the mechanisms governing hepatic AMPK activity [40]. The inflammatory response is another important factor influencing the onset and course of NAFLD [41]. Chronic inflammation not only exacerbates insulin resistance but also contributes to hepatic steatosis and fibrosis, which are key features of NAFLD. Pro-inflammatory cytokines such as the IL-1 family (IL-1F) and TNF-\(\alpha\) play significant roles in the regulation of inflammation-related insulin resistance [42; 43]. Specifically, TNF-\(\alpha\) contributes to the development of hepatic steatosis and IR in NAFLD and plays a critical role in metabolic inflammation by regulating the inflammatory process in the liver [43]. Metabolic inflammation, a hallmark of disorders such as obesity, type 2 diabetes, and NAFLD, is primarily driven by excessive nutrient intake, particularly dietary lipids [44]. Lipotoxicity, as manifested here, primarily occurs in organs involved in lipid metabolism, such as the liver, muscle, and adipose tissue. In particular, the degree of adipose tissue inflammation strongly correlates with the severity of liver inflammation in NAFLD [45]. Similarly, IL-18 is a critical mediator in hepatic inflammatory processes, influencing insulin resistance and fibrosis [43]. IL-18 acts through specific receptors and is characterized by a short half-life [46]. In particular, IL-18 is known to activate the nucleotide-binding and oligomerization domain-like receptor family (NLR) pyrin-domain-containing (NLRP) 3 inflammasome, which is implicated in the onset of type 2 diabetes [47]. In addition, IL-6 appears to be synthesized in response to liver damage, regulates the liver damage/regeneration process, and promotes insulin resistance, which impairs glucose homeostasis [48]. Our study discovered that the consumption of FGK suppresses the expression of inflammatory cytokines induced by high-calorie and high-fat diets. The anti-inflammatory activity of FGK observed in this study is similar to the results observed in our previous study on alcoholic liver injury [23]. Therefore, this study hypothesizes that the administration of FGK may contribute to the alleviation of NAFLD through the inhibition of inflammation. When these results are considered together, the fermentation process enhanced the bioactive compounds in kiwifruit, such as flavonoids and carotenoids, which exhibited significant anti-inflammatory and antioxidant effects [24; 25]. These enhanced compounds contributed to the improvement of HFD-induced NAFLD mice. In our HFD model, NAFLD is characterized by hyperlipidemia and hepatic steatosis, similar to NAFLD in humans. Mice fed an HFD and administered FGK showed significantly lower blood glucose levels and reduced weight gain, suggesting that FGK mitigates metabolic dysfunction associated with HFD consumption. The results also indicated a reduction of insulin resistance, as demonstrated by reductions in ALT and AST biomarkers that are associated with liver damage. FGK also modulated lipid metabolism by reducing TC, TG, and LDL levels, while increasing HDL levels, while increasing HDL levels, indicating its potential to improve overall lipid profiles in NAFLD models. Furthermore, in mice fed the HFD, FGK also appeared to activate the SIRT1/AMPK pathway in the liver, effectively inhibiting factors of activated inflammatory cytokines (Figure 9). These dual mechanisms--modulating lipid metabolism and suppressing inflammation--highlight FGK's unique therapeutic in addressing the complex pathophysiology of NAFLD.