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袖状胃切除术通过叉头框 O1（FoxO1）/脂联素 2（LCN2）通路对糖代谢的影响。

Effect of Sleeve Gastrectomy on Glycometabolism via Forkhead Box O1 (FoxO1)/Lipocalin-2 (LCN2) Pathway.

机构信息

Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China (mainland).

Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China (mainland).

出版信息

Med Sci Monit. 2020 Aug 26;26:e927458. doi: 10.12659/MSM.927458.

DOI:10.12659/MSM.927458
PMID:32845875
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7780888/
Abstract

BACKGROUND The mechanism by which sleeve gastrectomy (SG) improves glycometabolism has remained unclear so far. Increasing evidence has demonstrated that bone is a regulator of glucose metabolism, and osteoblast-derived forkhead box O1 (FoxO1) and lipocalin-2 (LCN2) are regulators of energy metabolism. The aim of this study was to investigate whether the FOXO1/LCN2 signaling pathway is involved in the anti-diabetic effect of SG. MATERIAL AND METHODS Insulin resistance was induced in Wistar rats, which were then intraperitoneally injected with streptozotocin to induce a type 2 diabetic state. Levels of fasting blood glucose, serum insulin, HbA1c, and LCN2 were analyzed at corresponding time points after SG and sham surgeries. The expressions of FOXO1, LCN2, and the melanocortin 4 receptor (MC4R) in bone and hypothalamus were detected by immunofluorescence. FOXO1 siRNA was applied to downregulate FOXO1 expression in osteoblasts of rats. The influence of FOXO1 gene on expression of LCN2 was investigated in cultured osteoblasts by western blot and PCR. RESULTS Glucose metabolism in the SG group was significantly improved. The LCN2 expression in bone in the SG group was higher than that in the sham group, whereas FOXO1 expression in the SG group was lower than that in the sham group. The binding rate of LCN2 and MC4R in the hypothalamus was also higher in the SG group compared with that in the sham group. The downregulation of FOXO1 expression in osteoblasts was accompanied by upregulation of LCN2 expression. CONCLUSIONS These results suggest that the FOXO1/LCN2 signaling pathway participates in the anti-diabetic effect of SG.

摘要

背景

迄今为止，袖状胃切除术（SG）改善糖代谢的机制仍不清楚。越来越多的证据表明，骨骼是葡萄糖代谢的调节剂，成骨细胞衍生的叉头框 O1（FoxO1）和脂联素-2（LCN2）是能量代谢的调节剂。本研究旨在探讨 FOXO1/LCN2 信号通路是否参与 SG 的抗糖尿病作用。

材料和方法

在 Wistar 大鼠中诱导胰岛素抵抗，然后通过腹腔注射链脲佐菌素诱导 2 型糖尿病状态。在 SG 和假手术相应时间点分析空腹血糖、血清胰岛素、HbA1c 和 LCN2 水平。通过免疫荧光检测骨和下丘脑的 FOXO1、LCN2 和黑皮质素 4 受体（MC4R）的表达。应用 FOXO1 siRNA 下调大鼠成骨细胞中 FOXO1 的表达。通过 Western blot 和 PCR 研究 FOXO1 基因对培养的成骨细胞中 LCN2 表达的影响。

结果

SG 组的糖代谢明显改善。SG 组骨中 LCN2 的表达高于假手术组，而 SG 组 FOXO1 的表达低于假手术组。与假手术组相比，SG 组下丘脑 LCN2 和 MC4R 的结合率也更高。成骨细胞中 FOXO1 表达下调伴随着 LCN2 表达上调。

结论

这些结果表明，FOXO1/LCN2 信号通路参与 SG 的抗糖尿病作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e0/7780888/7ca411ae9a05/medscimonit-26-e927458-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53e0/7780888/7ca411ae9a05/medscimonit-26-e927458-g008.jpg

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