N-carbamoyl aspartate reduced body weight by stimulating the thermogenesis of iBAT.

Uridine has formerly been shown to alleviate obesity and hepatic lipid accumulation. N-carbamoyl aspartate (NCA) provides carbon atoms to uridine in de novo pyrimidine biosynthesis pathway. However, whether NCA is involved in the lipid metabolism remains elusive. Here we showed that NCA supplementation significantly decreased (P < 0.05) serum cholesterol (CHOL), high-density lipoprotein (HDL), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) levels of mice, and significantly increased (P < 0.05) relative mRNA expression of genes related to the synthesis of pyrimidine nucleotides and polyunsaturated fatty acids. Besides, supplemented with NCA significantly decreased body weight and area under the curve (AUC), and increased body temperature in the high-fat diet fed mice. For further, relative protein expression of uridine monophosphate synthase (UMPS), sterol regulatory element-binding protein 1(SREBP-1) and phosphorylated hormone-sensitive triglyceride lipase (P-HSL) in the liver, and uncoupling protein 1 (UCP-1) in interscapular brown adipose tissue (iBAT) also showed upregulated in the high-fat diet fed mice. Thus, NCA promoted de novo synthesis of pyrimidine and polyunsaturated fatty acid, and reduced body weight by stimulating high-fat diet-induced thermogenesis of iBAT.

Beneficial effect of the short-chain fatty acid propionate on vascular calcification through intestinal microbiota remodelling.

BACKGROUND: Vascular calcification is a major cause of the high morbidity and mortality of cardiovascular diseases and is closely associated with the intestinal microbiota. Short-chain fatty acids (SCFAs) are derived from the intestinal microbiota and can also regulate intestinal microbiota homeostasis. However, it remains unclear whether exogenous supplementation with propionate, a SCFA, can ameliorate vascular calcification by regulating the intestinal microbiota. This study was conducted to explore the roles of propionate and the intestinal microbiota in the process of vascular calcification. METHODS: In total, 92 patients were enrolled consecutively as the observational cohort to analyse the relationship between SCFAs and vascular calcification in both blood and faecal samples. A rat model of vascular calcification was induced by vitamin D3 and nicotine (VDN) to validate the effect of propionate. Differences in the intestinal microbiota were analysed by 16S ribosomal RNA gene sequencing. Faecal microbiota transplantation and Akkermansia muciniphila transplantation experiments were performed to evaluate the functions of the intestinal microbiota. RESULTS: The results of the observational cohort study revealed that the levels of SCFAs (particularly propionate) in both blood and faecal samples independently correlated negatively with calcification scores (P < 0.01). To verify the activities of propionate, it was provided to VDN-treated rats, and oral or rectal propionate delivery reshaped the intestinal microbiota, resulted in elevated SCFA production, improved intestinal barrier function and alleviated inflammation, ultimately ameliorating vascular calcification. Furthermore, we demonstrated that transplantation of the propionate-modulated intestinal microbiota induced beneficial outcomes similar to those with oral or rectal propionate administration. Interestingly, linear discriminant analysis (LDA) effect size (LEfSe) revealed that oral or rectal propionate administration and propionate-modulated intestinal microbiota transplantation both enriched primarily Akkermansia. Subsequently, we demonstrated that Akkermansia supplementation could ameliorate VDN-induced vascular calcification in rats. CONCLUSIONS: Propionate can significantly ameliorate vascular calcification in VDN-treated rats, and this effect is mediated by intestinal microbiota remodelling. The findings in our study indicate that the intestinal tract-vessel axis is a promising target for alleviating vascular calcification. Video Abstract.

[In vivo and in vitro effect of peptide HP-6 derived from donkey serum albumin on hematopoietic system].

OBJECTIVE: By bioinformatics method, the effect in hematopoietic system of bioactive peptide HP-6, which was obtained from donkey serum albumin and is one of the major protein components from donkey-hide gelatin, was investigated. METHOD: Human bone marrow nucleated cells (hBMNCs) and murine bone marrow stromal cells (mBMSCs) were separated and cultured with different concentration of peptide HP-6 (0.000 15, 0.001 5, 0.015, 0.15, 1.5 micromol x L(-1)). The effect on promoting proliferation of cells related to hematopoiesis in bone morrow was detected and the ultrastructure of cells after treated by HP-6 was observed through transmission electron microscope. Hemorrhage anemia mouse model and anemia mouse model induced by cyclophosphamide were established, and randomly divided into peptide HP-6 groups which were administered respectively with different doses (1, 0.1, 0.01 mg x kg(-1)) by gavage, and control group which was administered with PBS by gavage. Peripheral blood components of all mice and bone morrow cells (BMC) number of mice induced by cyclophosphamide were evaluated. RESULT: Peptide HP-6 could concentration-related promote the proliferation of hBMNCs and mBMSCs, hBMNCs got the highest reproduction rate of 152.11% and mBMSCs also got 63.52% with the concentration of 0.15 micromol x L(-1), then the reproduction rate decreased while the concentration kept increasing. The transmission electron microscope showed that ultrastructure of cells was normal after treated by HP-6.1 mg x kg(-1) peptide HP-6 significantly increased peripheral platelet and protected mouse morrow injured by cyclophoshamide. 0.1 mg x kg(-1) peptide HP-6 significantly increased peripheral platelet with relative growth rate of 77.65%, increased peripheral white blood cells count and peripheral red blood cells count, also could protect mouse peripheral blood after treated by chemotherapeutics. CONCLUSION: Peptide HP-6 could promote the proliferation of cells related to hematopoietic system, enhance mouse hemopoiesis function and the resistance to chemotherapeutic injury.