The role of roof plate-specific spondins in liver homeostasis and disease

As evolutionarily conserved signals,roof plate-specific spondins(R-spondins;RSPOs)are a family with four members(RSPO1e4)exerting distinctly different functions.RSPOs have five receptors and correlate with different signaling pathways through these receptors and then perform various functions.Moreover,their best-known molecular function is the capacity to enhance WNT signaling pathways,which play critical roles in several processes.A recent study shows that RSPOs not only potentiate the WNT/beta(b)-catenin signaling pathway but are also involved in the WNT/planar cell polarity signaling pathway.RSPOs influence liver homeostasis and the development of multiple liver diseases.RSPO1 increases cell proliferation,protects hepatocytes from injury,improves liver regenerative potential,and affects liver metabolic zonation.RSPO2 not only regulates proliferation-associated genes and promotes differentiation in the liver but also participates in liver fibrosis through the WNT/b-catenin signaling pathway.RSPO3 is a key determinant of proper liver function,such as promoting hepatocyte regeneration and maintaining liver zonation.RSPO3 is upregulated in liver fibrosis and livers of patients with nonalcoholic steatohepatitis.Besides,RSPO2 and RSPO3 are confirmed as oncogenes and involved in the occurrence of liver cancer.The role of RSPO4 in the liver remains unclear.In this review,the structural and biochemical properties of RSPOs and their receptors and their roles in liver homeostasis and disease are summarized.

The efficiency and safety evaluation of hemoglobin hydrolysate as a non-heme iron fortifier

Hemoglobin hydrolysate is derived from the enzymatic degradation of hemoglobin.This work aimed to evaluate whether hemoglobin hydrolysate promotes the absorption of non-heme iron and the safety of absorbed iron in mice by analyzing the iron binding content,iron circulation,and liver homeostasis.We found that hemoglobin hydrolysate promoted the absorption of non-heme iron with high efficiency in duodenum by spontaneously binding non-heme iron during digestion,and increased hepatic iron content by up-regulating divalent metal transporter 1,zinc transporter 14,but hepatic iron content only increased at 3 weeks.Duodenal iron entered the blood through ferroportin without restriction at 3 weeks,and excessive iron entered the liver and then affected the hepatocyte membranes permeability and lipid synthesis through oxidative stress.With the prolongation of dietary intervention,the up-regulated hepcidin acted on the ferroportin to restrict excess iron from entering the blood,and then the hepatic homeostasis recovered.In addition,hemoglobin hydrolysate enhanced the hepatic antioxidant capacity.Taken together,hemoglobin hydrolysate has a strong ability to promote the absorption of non-heme iron in vivo,and the absorbed iron is relatively safe due to the regulation of hepcidin.