Pharmacology Department, Biomedical Sciences Institute (ICB), São Paulo 05508-000, SP, Brazil.
Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences (FCF), University of São Paulo (USP), São Paulo 05508-000, SP, Brazil.
Int J Mol Sci. 2023 Oct 14;24(20):15190. doi: 10.3390/ijms242015190.
Neurolysin oligopeptidase (E.C.3.4.24.16; Nln), a member of the zinc metallopeptidase M3 family, was first identified in rat brain synaptic membranes hydrolyzing neurotensin at the Pro-Tyr peptide bond. The previous development of C57BL6/N mice with suppression of Nln gene expression (Nln), demonstrated the biological relevance of this oligopeptidase for insulin signaling and glucose uptake. Here, several metabolic parameters were investigated in Nln and wild-type C57BL6/N animals (WT; n = 5-8), male and female, fed either a standard (SD) or a hypercaloric diet (HD), for seven weeks. Higher food intake and body mass gain was observed for Nln animals fed HD, compared to both male and female WT control animals fed HD. Leptin gene expression was higher in Nln male and female animals fed HD, compared to WT controls. Both WT and Nln females fed HD showed similar gene expression increase of dipeptidyl peptidase 4 (DPP4), a peptidase related to glucagon-like peptide-1 (GLP-1) metabolism. The present data suggest that Nln participates in the physiological mechanisms related to diet-induced obesity. Further studies will be necessary to better understand the molecular mechanism responsible for the higher body mass gain observed in Nln animals fed HD.
神经溶解酶寡肽酶（E.C.3.4.24.16；Nln），锌金属肽酶 M3 家族的成员，最初在大鼠脑突触膜中被发现，可在脯氨酸-酪氨酸肽键处水解神经降压素。先前通过抑制 Nln 基因表达（Nln）培育出 C57BL6/N 小鼠，证明了这种寡肽酶在胰岛素信号和葡萄糖摄取中的生物学相关性。在这里，研究了 Nln 和野生型 C57BL6/N 动物（WT；n = 5-8）的几种代谢参数，雄性和雌性，分别用标准（SD）或高热量饮食（HD）喂养七周。与雄性和雌性 WT 对照动物相比，用 HD 喂养的 Nln 动物表现出更高的食物摄入量和体重增加。用 HD 喂养的 Nln 雄性和雌性动物的瘦素基因表达高于 WT 对照动物。用 HD 喂养的 WT 和 Nln 雌性动物的二肽基肽酶 4（DPP4）基因表达均增加，DPP4 是一种与胰高血糖素样肽-1（GLP-1）代谢相关的肽酶。目前的数据表明，Nln 参与了与饮食诱导肥胖相关的生理机制。需要进一步的研究来更好地理解导致用 HD 喂养的 Nln 动物体重增加的分子机制。
