LCN2 blockade mitigating metabolic dysregulation and redefining appetite control in type 2 diabetes.

IF 3.2 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Metabolic brain disease Pub Date : 2025-01-14 DOI:10.1007/s11011-024-01454-0

Cifuentes-Mendiola Saúl Ernesto, Sólis-Suarez Diana Laura, Pérez-Martínez Isaac Obed, Andrade-González Rey David, García-Gama Jahaziel Eloy, García-Hernández Ana Lilia

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引用次数: 0

Abstract

LCN2 has an osteokine important for appetite regulation; in type 2 diabetes (T2D) it is not known whether appetite regulation mediated by LCN2 in the brain is altered. In this work, we focus on exploring the role of blocking LCN2 in metabolic health and appetite regulation within the central nervous system of mice with T2D.

Material and methods: 4-week-old male C57BL/6 mice were used, divided into four experimental groups: intact, T2D, TD2/anti-LCN2, and T2D/IgG as isotype control. T2D was induced by low doses of streptozotocin and a high-carbohydrate diet. LCN2 blockade was performed by intraperitoneal administration of a polyclonal anti-LCN2 antibody. We analyzed metabolic parameters, food intake, feeding patterns, and serum LCN2 and leptin concentrations. In another group of intact or T2D mice, we analyzed the effect of blocking LCN2 and recombinant LCN2 on food consumption in a fasting-refeeding test and, the expression of cFOS and LCN2 in brain sections, specifically in the hypothalamus, piriform cortex, visceral area, arcuate nucleus and caudate-putamen.

Results: T2D caused an increase in serum LCN2, without alterations in Ad libitum feeding, but with changes in the feeding pattern associated with alterations in LCN2-cFOS signalling in hypothalamic and non-hypothalamic brain regions. Blocking LCN2 improved metabolic parameters, increased Ad libitum feeding, and restored the feeding pattern after fasting, which is associated with enhanced LCN2 signalling in the brain.

Conclusions: Blocking LCN2 restores metabolic health and normalizes the pattern of food consumption by normalizing LCN2 signalling in different brain regions.

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LCN2阻断缓解2型糖尿病代谢失调和重新定义食欲控制。

LCN2具有对食欲调节重要的骨因子；在2型糖尿病（T2D）中，大脑中LCN2介导的食欲调节是否被改变尚不清楚。在这项工作中，我们重点探索阻断LCN2在T2D小鼠中枢神经系统代谢健康和食欲调节中的作用。材料与方法：选用4周龄雄性C57BL/6小鼠，分为4个实验组：完整组、T2D组、TD2/抗lcn2组、T2D/IgG组为同型对照。低剂量链脲佐菌素和高碳水化合物饮食诱导T2D。通过腹腔注射一种多克隆抗LCN2抗体来阻断LCN2。我们分析了代谢参数、食物摄入、喂养方式和血清LCN2和瘦素浓度。在另一组完整或T2D小鼠中，我们分析了阻断LCN2和重组LCN2对禁食-再喂养试验中食物消耗的影响，以及大脑切片中cFOS和LCN2的表达，特别是在下丘脑、梨状皮质、内脏区、弓形核和尾状壳核。结果：T2D引起血清LCN2升高，但不改变自由摄食，但摄食模式的改变与下丘脑和非下丘脑脑区LCN2- cfos信号的改变有关。阻断LCN2改善了代谢参数，增加了随意摄食，并恢复了禁食后的摄食模式，这与大脑中LCN2信号的增强有关。结论：阻断LCN2可恢复代谢健康，并通过使不同脑区的LCN2信号正常化，使食物消费模式正常化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Metabolic brain disease 医学-内分泌学与代谢

CiteScore

5.90

自引率

5.60%

发文量

248

审稿时长

6-12 weeks

期刊介绍： Metabolic Brain Disease serves as a forum for the publication of outstanding basic and clinical papers on all metabolic brain disease, including both human and animal studies. The journal publishes papers on the fundamental pathogenesis of these disorders and on related experimental and clinical techniques and methodologies. Metabolic Brain Disease is directed to physicians, neuroscientists, internists, psychiatrists, neurologists, pathologists, and others involved in the research and treatment of a broad range of metabolic brain disorders.