Neuropeptide Y-Mediated Gut Microbiota Alterations Aggravate Postmenopausal Osteoporosis.

Postmenopausal osteoporosis (PMO) is often accompanied by neuroendocrine changes in the hypothalamus, which closely associates with the microbial diversity, community composition, and intestinal metabolites of gut microbiota (GM). With the emerging role of GM in bone metabolism, a potential neuroendocrine signal neuropeptide Y (NPY) mediated brain-gut-bone axis has come to light. Herein, it is reported that exogenous overexpression of NPY reduced bone formation, damaged bone microstructure, and up-regulated the expressions of pyroptosis-related proteins in subchondral cancellous bone in ovariectomized (OVX) rats, but Y1 receptor antagonist (Y1Ra) reversed these changes. In addition, it is found that exogenous overexpression of NPY aggravated colonic inflammation, impaired intestinal barrier integrity, enhanced intestinal permeability, and increased serum lipopolysaccharide (LPS) in OVX rats, and Y1Ra also reversed these changes. Most importantly, NPY and Y1Ra modulated the microbial diversity and changed the community composition of GM in OVX rats, and thereby affecting the metabolites of GM (e.g., LPS) entering the blood circulation. Moreover, fecal microbiota transplantation further testified the effect of NPY-mediated GM changes on bone. In vitro, LPS induced pyroptosis, reduced viability, and inhibited differentiation of osteoblasts. The study demonstrated the existence of NPY-mediated brain-gut-bone axis and it might be a novel emerging target to treat PMO.

The Expression of Zinc Transporters Changed in the Intestine of Weaned Pigs Exposed to Zinc Chitosan Chelate.

This study was conducted to investigate the effect of zinc chitosan chelate (CS-Zn) on zinc transporter expression and content of tissue zinc in weaned piglets. A total of 90 weaned pigs (Duroc × Landrace × Yorkshire) were randomly allocated to treatment groups with supplementation of 100 mg/kg zinc as ZnSO4, 100 mg/kg zinc as mixture of ZnSO4 and chitosan, or 100 mg/kg zinc as CS-Zn, respectively. After 30 days of trial, 18 piglets (six pigs per treatment) were killed and the samples of duodenal mucosa were taken for analysis of zinc transporter mRNA expressions and protein abundance. The results show that CS-Zn more effectively increases (p < 0.05) the average daily gain (ADG) and serum zinc concentration. Zinc concentration in the liver and kidney did not differ between treatments. The mRNA expressions of ZnT1, ZIP4, and ZIP5 in CS-Zn treatment were all upregulated (p < 0.05) than ZnSO4 or mixture of ZnSO4 and chitosan groups. ZnT1 abundance was greater (p < 0.05) with CS-Zn as compared with ZnSO4 and mixture of ZnSO4 and chitosan treatments, whereas ZIP4 and ZIP5 abundance was higher (p < 0.05) in ZnSO4 group. The results indicate that CS-Zn is more effective in serum zinc accumulation, and it might regulate zinc homeostasis by affecting zinc transporter mRNA expression and absorption mechanism might be different with ZnSO4.

Chitosan-Zn chelate increases antioxidant enzyme activity and improves immune function in weaned piglets.

This experiment was performed in order to investigate the effects of chitosan-Zn chelate (CS-Zn) on activities of antioxidant enzymes and immune function in weaned piglets. One hundred and twenty weaned piglets (Duroc × Landrace × Yorkshire) with 7.12 ± 0.25 kg body weight were allotted to four treatments. A basal diet without Zn supplementation was used as control group. The other three treatments were fed the control diet supplemented with 100 mg/kg Zn as ZnSO4, 100 mg/kg Zn as CS-Zn, 100 mg/kg Zn as ZnSO4 and chitosan (the content of chitosan was the same as that of CS-Zn), respectively. The feeding trial lasted 30 days. Spleen index of pigs fed dietary CS-Zn was higher (p < 0.05) than that of control pigs. Thymus index and lymph node index did not differ among the pigs fed any diets (p > 0.05). T-AOC levels, Cu-ZnSOD, and GSH-PX activities in serum or liver of the pigs receiving CS-Zn diet were higher than those of the pigs fed CS+ZnSO4 or ZnSO4 diets (p < 0.05). These pigs fed dietary CS-Zn also showed lower MDA content in liver compared with the pigs fed other diets (p < 0.05). Serum IgA, complement 3, and complement 4 levels of pig fed dietary CS-Zn was higher than those of the pigs fed other diets (p < 0.05). Supplemental dietary Zn did not change serum IgG and IgM levels (p > 0.05). The ALP activity of pigs fed dietary CS-Zn was higher than those of the pigs fed other three diets (p < 0.05). No significant differences were founded in serum GOT or GPT activities of pigs fed dietary Zn (p > 0.05). The results of the present study indicated that chitosan-Zn chelate could increase antioxidant capacity and improve immune function in weaned piglets compared with ZnSO4 or chitosan.

Chitosan-zinc chelate improves intestinal structure and mucosal function and decreases apoptosis in ileal mucosal epithelial cells in weaned pigs.

The present study was conducted to investigate the effects of chitosan (CS)-Zn on intestinal morphology, mucosal epithelial cell apoptosis and mucosal immune function in weanling pigs. A total of 150 weanling barrows with a body weight of 7.2 kg were randomly allocated into five groups. A basal diet without Zn supplementation was used as the control and other four groups were fed the control diet supplemented with 50 or 100 mg/kg of Zn as CS-Zn, 100 mg/kg of Zn as ZnSO4 and 3000 mg/kg of Zn as ZnO, respectively. The feeding trial lasted for 28 d. The results showed that serum diamine oxidase activities, d-lactate levels and endotoxin contents were lower in pigs fed dietary 100 mg/kg of Zn as CS-Zn or 3000 mg/kg of Zn as ZnO than in pigs fed the control or 100 mg Zn/kg as ZnSO4 diet. The ratios of the villus height:crypt depth of the duodenum, jejunum and ileum were higher in pigs that received 100 mg/kg of Zn as CS-Zn or a high level of Zn as ZnO than in pigs fed the control diet. Moreover, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL)-stained ileal epithelial cells were found in the control group, and apoptotic cells did not appear prominently in pigs that received the 100 mg/kg of CS-Zn or ZnO diet. Secretory IgA concentration in ileal mucus was increased in the dietary group that received 100 mg/kg of CS-Zn or ZnO. These results indicated that dietary 100 mg CS-Zn/kg had similar biological effects to dietary 3000 mg ZnO/kg on intestinal morphology, mucosal epithelial cell apoptosis and mucosal immune function.