Effects of Iron and Onion Supplementation on Advanced Glycation End Products Metabolism in Obese Rat Model

Dysregulated iron metabolism is a hallmark of obesity and nonalcoholic fatty liver disease (NAFLD) but the underlying mechanisms remain unclear. Onions are polyphenol-rich foods which are known to reduce liver inflammation and regulate iron absorption. Our recent clinical study (33 controls and 137 NAFLD) showed that serum soluble (s) CD163 and free hemoglobin (Hb) are independent predictors of Nε-(carboxymethyl)lysine (CML), a major antigenic advanced glycation end products (AGEs) structure. Multivariate logistic regression analysis showed that serum CML-sCD163 or CML-free Hb levels independently predict NAFLD (MOST 104－2311－B038－005 end report). Our recent animal study demonstrated that 10 weeks of pharmacological doses of ferric citrate supplementation to rats with streptozotocin-induced diabetes increase liver steatosis, lipid peroxidation, endoplasmic reticulum (ER) stress, and accumulation of AGEs. Our results raise the possibility that altered AGE metabolism is likely due to the combined effects of increased hepatic lipid and iron accumulation on AGE detoxification. The broad aim of this study is to investigate effects of iron and onion supplementation on AGEs metabolism in diet induced obese rats. This will be accomplished through experiments involving high fat diet induced NAFLD rat model: (1) to dissect molecular mechanisms of iron supplementation on AGEs metabolism, (2) to evaluate effects of onion supplementation on iron-fat mediated ER stress and AGEs-RAGE pathways, and (3) in vitro experiment to delineate the role of CD163+macrophages on iron-fat mediated endogenous AGEs formation and degradation. Understanding how obesity-related inflammation affect iron metabolism will advance our knowledge on how to treat NAFLD patients and provide better care for NAFLD management in practice.