Djulis Hull Enhances the Efficacy of Ferric Citrate Supplementation via Restoring Normal Iron Efflux through the IL-6-Hepcidin-Ferroportin Pathway in High-Fat-Diet-Induced Obese Rats

J Agric Food Chem. 2023 Nov 8;71(44):16691-16701. doi: 10.1021/acs.jafc.3c02826. Epub 2023 Oct 25.

Abstract

Obesity-related functional iron disorder remains a major nutritional challenge. We evaluated the effects of djulis hull (DH) on iron metabolism in 50% high-fat-diet-induced obese rats supplemented with ferric citrate (2 g iron/kg diet) for 12 weeks. DH supplementation (5, 10, 15% dry weight/kg diet) significantly increased serum and hepatic iron but decreased appetite hormones, body weight, hepcidin, and liver inflammation (all p < 0.05). The Spearman correlation showed that appetite hormones were negatively associated with iron but positively correlated with liver hepcidin (all p < 0.05). A Western blot analysis showed that DH significantly downregulated hepatic hepcidin through the IL-6-JAK-STAT3 and enhanced ferroportin (Fpn) via the Keap1-Nrf2 and PHD2-HIF-2α. An in vitro study revealed that major bioactive compounds of DH, hexacosanol, and squalene suppressed LPS-induced IL-6 and hepcidin but enhanced Fpn expression in activated THP-1 cells. In conclusion, DH may exert nutraceutical properties for the treatment of functional iron disorder and restoration of iron efflux may have beneficial effects on weight control.

Keywords: appetite hormones; body weight; djulis hull; ferric citrate; iron metabolism; obesity.

MeSH terms

  • Animals
  • Dietary Supplements
  • Hepcidins* / genetics
  • Hepcidins* / metabolism
  • Hormones
  • Interleukin-6* / genetics
  • Interleukin-6* / metabolism
  • Iron / metabolism
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • NF-E2-Related Factor 2 / metabolism
  • Obesity / drug therapy
  • Obesity / etiology
  • Rats

Substances

  • ferric citrate
  • Hepcidins
  • metal transporting protein 1
  • Interleukin-6
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • Iron
  • Hormones