Paradoxical role of lipocalin-2 in metabolic disorders and neurological complications
Paradoxical role of lipocalin-2 in metabolic disorders and neurological complications
复制标题
脂质运载蛋白-2在代谢紊乱和神经系统并发症中的作用
DOI：
10.1016/j.bcp.2019.113626
复制
发表时间：
2019-11-01
影响因子：
5.8
通讯作者：
Suk, Kyoungho
中科院分区：
文献类型：
--
作者：
Bhusal, Anup;Rahman, Md Habibur;Suk, Kyoungho
脂质运载蛋白-2（LCN 2），也称为24 p3和中性粒细胞明胶酶相关脂质运载蛋白（NGAL），是一种25 kDa的分泌蛋白，与各种代谢和炎症性疾病有关。早期的研究表明LCN 2的保护功能，其中它作为一种抑菌剂，与细菌竞争铁结合的铁载体。然而，LCN 2的有害和有益作用最近在代谢和神经炎性疾病中均有记载。如在糖尿病和肥胖症中观察到的，代谢性炎症与人类和啮齿动物的血浆和几种组织中的LCN 2的上调密切相关，表明其促糖尿病和促肥胖作用。相反，其他研究暗示LCN 2的抗糖尿病和抗肥胖作用，由此LCN 2基因的缺陷导致胰岛素敏感性受损并增强高脂肪饮食诱导的脂肪膨胀。LCN 2的类似双重作用也已在神经系统疾病的各种动物模型中报道。在这些混合的发现中，没有实验证据可以解释为什么LCN 2在各种研究中表现出如此不同的作用。这场辩论需要解决（或调和），关于这一专题的综合观点是可取的。在此，我们试图通过回顾LCN 2在代谢紊乱中的最新发现来解决这个问题，并评估LCN 2双重作用的潜在细胞或分子机制。我们进一步讨论了靶向LCN 2作为代谢紊乱和神经系统并发症的潜在治疗策略的可能性和挑战。
Lipocalin-2 (LCN2), also known as 24p3 and neutrophil gelatinase-associated lipocalin (NGAL), is a 25-kDa secreted protein implicated in various metabolic and inflammatory diseases. Early studies suggest the protective function of LCN2 in which it acts as a bacteriostatic agent that competes with bacteria for iron-bound siderophores. However, both detrimental and beneficial roles of LCN2 have recently been documented in metabolic and neuroinflammatory diseases. Metabolic inflammation, as observed in diabetes and obesity, has been closely associated with the upregulation of LCN2 in blood plasma and several tissues in both humans and rodents, suggesting its pro-diabetic and pro-obesogenic role. On the contrary, other studies imply an anti-diabetic and anti-obesogenic role of LCN2 whereby a deficiency in the Lcn2 gene results in the impairment of insulin sensitivity and enhances the high-fat-diet-induced expansion of fat. A similar dual role of LCN2 has also been reported in various animal models for neurological disorders. In the midst of these mixed findings, there is no experimental evidence to explain why LCN2 shows such a contrasting role in the various studies. This debate needs to be resolved (or reconciled) and an integrated view on the topic is desirable. Herein, we attempt to address this issue by reviewing the recent findings on LCN2 in metabolic disorders and assess the potential cellular or molecular mechanisms underlying the dual role of LCN2. We further discuss the possibilities and challenges of targeting LCN2 as a potential therapeutic strategy for metabolic disorders and neurological complications.