Effect of sterol regulatory element binding protein 1c expression on intestinal gluconeogenesis in mice

Linlin ZHANG; Yuxi XIAO; Bingyao LIU; Hongting ZHENG; Xiaoyu LIAO

doi:10.16016/j.2097-0927.202308033

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Effect of sterol regulatory element binding protein 1c expression on intestinal gluconeogenesis in mice

Basic Medicine | 更新时间：2026-01-09

- Effect of sterol regulatory element binding protein 1c expression on intestinal gluconeogenesis in mice
- Journal of Army Medical University Vol. 46, Issue 5, Pages: 403-409(2024)
- 作者机构：
  
  400037 重庆，陆军军医大学(第三军医大学)第二附属医院内分泌科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(82370815);General Program of Natural Science Foundation of Chongqing(cstc2021jcyj-msxmX0465);the Incubation Project of Young Doctoral Talent Program of the Second Affiliated Hospital of Army Medical University(2022YQB057)
- DOI：10.16016/j.2097-0927.202308033
  CLC： R322.45;R329.26;R394.1
- Received：10 August 2023，
  
  Revised：2023-09-22，
  
  Published：15 March 2024
- 稿件说明：
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Linlin ZHANG, Yuxi XIAO, Bingyao LIU, et al. Effect of sterol regulatory element binding protein 1c expression on intestinal gluconeogenesis in mice[J]. Journal of Army Medical University, 2024, 46(5): 403-409.
DOI：

Linlin ZHANG, Yuxi XIAO, Bingyao LIU, et al. Effect of sterol regulatory element binding protein 1c expression on intestinal gluconeogenesis in mice[J]. Journal of Army Medical University, 2024, 46(5): 403-409. DOI： 10.16016/j.2097-0927.202308033.

摘要

目的

研究固醇调节元件结合蛋白1c(sterol regulatory element binding protein 1c

SREBP1c)对肠道糖异生的调控作用。

方法

饥饿处理C57BL/6小鼠、

SREBP

纯合敲除型(SREBP1c-KO)和同窝野生型(SREBP1c-WT)小鼠，通过qPCR、Western blot检测糖异生途径限速酶葡萄糖-6-磷酸酶(glucose-6-phosphatase catalytic

G6PC)和磷酸烯醇式丙酮酸羧激酶(phosphoenolpyruvate carboxykinase 1

PCK1)在肝脏、空肠和回肠组织中的表达水平；在肠上皮细胞CaCo-2中过表达或敲低SREBP1c，检测细胞内G6PC和PCK1表达水平。

结果

饥饿处理后，C57BL/6小鼠空肠、回肠组织中G6PC、PCK1和SREBP1c表达水平均显著增加(

＜0.05)。

SREBP

基因敲除后，小鼠空肠、回肠组织中由饥饿诱导的糖异生限速酶G6PC和PCK1的表达明显下调(

＜0.05)。在肠上皮细胞CaCo-2中过表达SREBP1c，可显著上调糖异生途径关键酶G6PC和PCK1的表达，促进细胞内葡萄糖的产生(

＜0.05)；反之，敲低SREBP1c的表达，可明显下调G6PC和PCK1，抑制细胞内葡萄糖的产生(

＜0.05)。

结论

饥饿状态下，SREBP1c可调控肠上皮细胞中糖异生限速酶G6PC和PCK1的表达，进而影响葡萄糖的生成，表明SREBP1c可能参与肠道糖异生的调控，机制有待进一步探索。

Abstract

Objective

To investigate the regulation role of sterol regulatory element binding protein 1c (SREBP1c) in intestinal gluconeogenesis.

Methods

After C57BL/6 mice

and SREBP1c homozygous knockout (SREBP1c-KO) and littermate wild-type (SREBP1c-WT) mice were fasted for 48 h

qPCR and Western blotting were used to detect the expression of rate-limiting gluconeogenic genes glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1) in the liver

jejunum and ileum tissues at mRNA and protein levels. After overexpression or knockdown of SREBP1c in the intestinal epithelial cell line CaCo-2

the expression levels of G6PC and PCK1 were measured.

Results

The expression levels of G6PC

PCK1

and SREBP1c were significantly increased in the jejunum and ileum tissues of C57BL/6 mice after fasting (

0.05). In SREBP1c-KO mice

fasting treatment induced obviously inhibited expression of G6PC and PCK1 in the jejunum and ileum tissues (

0.05). Overexpression of SREBP1c significantly upregulated the expression levels of G6PC and PCK1

and promoted the production of glucose in CaCo-2 cells (

0.05). Conversely

knocking SREBP1c down resulted in down-regulation of G6PC and PCK1 and suppressed production of glucose in CaCo-2 cells (

0.05).

Conclusion

Under fasting

SREBP1c is involved in regulation of G6PC and PCK1 in intestinal epithelial cells

and thus affects glucose production. It indicates that SREBP1c might be involved in the regulation of intestinal gluconeogenesis

and the mechanism needs further exploration.

关键词

Keywords

references

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