Faculty of Chemical Technology , University of Chemistry and Technology Prague , Technická 5 , 166 28 , Prague 6 , Czech Republic.
Institute of Organic Chemistry and Biochemistry , Czech Academy of Sciences , Flemingovo nám. 2 , 166 10 , Prague 6 , Czech Republic.
J Proteome Res. 2019 Apr 5;18(4):1735-1750. doi: 10.1021/acs.jproteome.8b00964. Epub 2019 Mar 11.
In this study, the combination of metabolomics and standard biochemical and biometric parameters was used to describe the metabolic effects of diet-induced obesity and its treatment with the novel antiobesity compound palm-PrRP31 (palmitoylated prolactin-releasing peptide) in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). The results showed that SHR on a high-fat (HF) diet were normoglycemic with obesity and hypertension, while WKY on the HF diet were normotensive and obese with prediabetes. NMR-based metabolomics revealed mainly several microbial cometabolites altered by the HF diet, particularly in urine. The HF diet induced similar changes in both models. However, two groups of genotype-specific metabolites were defined: metabolites specific to the genotype at baseline (e.g., 1-methylnicotinamide, phenylacetylglycine, taurine, methylamine) and metabolites reacting specifically to the HF diet in individual genotypes (2-oxoglutarate, dimethylamine, N-butyrylglycine, p-cresyl sulfate). The palm-PrRP31 lowered body weight and improved biochemical and biometric parameters in both strains, and it improved glucose tolerance in WKY rats on the HF diet. In urine, the therapy induced significant decrease of formate and 1-methylnicotinamide in SHR and alanine, allantoin, dimethylamine, and N-butyrylglycine in WKY. Altogether, our study confirms the effectiveness of palm-PrRP31 for antiobesity treatment.
在这项研究中，我们结合代谢组学和标准生化及生物计量参数，描述了饮食诱导肥胖及其治疗的代谢效应，所用的新型减肥药是棕榈酰化促乳素释放肽（palmitoylated prolactin-releasing peptide），研究对象是自发性高血压大鼠（SHR）和正常血压 Wistar 京都大鼠（WKY）。结果表明，高脂肪（HF）饮食喂养的 SHR 血糖正常，但肥胖伴高血压，而 HF 饮食喂养的 WKY 血压正常，但肥胖且有前驱糖尿病。基于 NMR 的代谢组学显示，主要有几种微生物共代谢物受 HF 饮食改变，尤其是在尿液中。HF 饮食在两种模型中引起了相似的变化。然而，我们定义了两组具有基因型特异性的代谢物：在基线时具有基因型特异性的代谢物（例如 1-甲基烟酰胺、苯乙酰甘氨酸、牛磺酸、甲胺）和在个体基因型中对 HF 饮食有特异性反应的代谢物（2-氧戊二酸、二甲胺、N-丁酰甘氨酸、对甲酚硫酸盐）。棕榈酰化促乳素释放肽降低了两种品系的体重和改善了生化及生物计量参数，并改善了 HF 饮食喂养的 WKY 大鼠的葡萄糖耐量。在尿液中，治疗导致 SHR 中甲酸和 1-甲基烟酰胺显著减少，WKY 中丙氨酸、尿囊素、二甲胺和 N-丁酰甘氨酸减少。总之，我们的研究证实了棕榈酰化促乳素释放肽治疗肥胖的有效性。
