Circulating Iron Levels Interaction with Central Obesity on the Risk of Nonalcoholic Fatty Liver Disease: A Case–Control Study in Southeast China

Abstract

Objectives: We aimed to evaluate the associations between body iron stores and the risk of nonalcoholic fatty liver disease (NAFLD) in a Chinese population and explore whether this effect may be modified by other factors. Methods: A 1: 1 frequency-matched case–control study was conducted, including 482 NAFLD cases and 490 gender- and age-matched controls. Serum levels of ferritin, hepcidin, and C-reactive protein were measured. Results: Multivariate logistic regression analysis showed that hepcidin was not associated with NAFLD risk; however, elevated serum ferritin was significantly associated with increased risk of NAFLD (adjusted OR 1.619, 95% CI 1.158–2.267), and hepcidin:ferritin ratio was significantly associated with decreased risk of NAFLD ­(OR­_adjusted 0.702, 95% CI 0.501–0.984). When stratified by gender, a significant association was found between elevated serum ferritin and hepcidin:ferritin ratio and NAFLD only for women (OR_adjusted 2.131, 95% CI 1.151–3.944 and OR_adjusted 0.414, 95% CI 0.219–0.781, respectively). A significant multiplicative interaction between central obesity and elevated serum hepcidin was observed (p < 0.05). Conclusions: Elevated serum ferritin and hepcidin:ferritin ratio are associated with NAFLD in a Chinese population. Although serum hepcidin is not associated with NAFLD, it may augment the risk effect of central obesity on NAFLD.

Predictive Value of Serum Ferritin in Combination with Alanine Aminotransferase and Glucose Levels for Noninvasive Assessment of NAFLD: Fatty Liver in Obesity (FLiO) Study

“…In line with our results, Ryan et al reported a strong association between ferritin and hepatic iron content by MRI in 129 participants with NAFLD [39]. Scientific evidences have shown that increased iron stores are intimately connected to β-cell dysfunction, impaired glucose metabolism, type 2 diabetes, DNA damage, and lipid peroxidation [24,36,37]. The main mechanism proposed is that iron promotes oxidative stress reactions resulting in cellular damage [14,15].…”

“…Hepatocytes constitute the major parenchymal iron storage pool and contain large amounts of ferritin, the primary iron storage protein [35]. Iron is an essential but potentially toxic element that may promote the onset and progression of NAFLD by increasing oxidative stress and altering insulin signaling and lipid metabolism [14,15,36,37]. Iron overload is observed in approximately one-third of adults with NAFLD [38].…”

Association of Meat Consumption With NAFLD&nbsp;Risk and Liver-related Biomarkers in Older Chinese: A Cross-sectional Study

“…Hence, it's plausible that increased hepatic lipid accumulation and insulin resistance play a substantial role in the relationship of meat intakes with the development of NAFLD. In addition, a study by Avila et al found that red meat was positively relevant to serum ferritin [32], which can increase the risk of NAFLD [33,34]. Fried food will produce some hazardous chemicals, such as advanced glycation end products and trans fatty acids [35,36], which were reported to play a critical role in NAFLD [37,38].…”

Association between Different Animal Protein Sources and Liver Status in Obese Subjects with Non-Alcoholic Fatty Liver Disease: Fatty Liver in Obesity (FLiO) Study

“…However, in inflammatory conditions ferritin concentrations are increased and it is synthesized as an acute phase protein, acting as a pro-inflammatory molecule capable of inducing liver damage. [33,35,36,37]. The potential anti-inflammatory effect and antioxidant capacity of omega-3 PUFAs [38], might ameliorate ferritin pro-oxidant and pro-inflammatory activity, although the exact molecular pathways are yet to be elucidated.…”

“…The liver is the principal iron-storage organ and plays a central role in iron metabolism [4,35]. Increased hepatic iron concentrations are associated with metabolic alterations including insulin resistance and type 2 diabetes [15].…”