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长寿生长激素受体基因敲除小鼠移植内脏脂肪对胰岛素信号的作用。

The role of transplanted visceral fat from the long-lived growth hormone receptor knockout mice on insulin signaling.

机构信息

College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, 6900 Lake Nona Blvd., Orlando, FL, 32827, USA.

Faculdade de Nutrição, Universidade Federal de Pelotas, Pelotas, RS, Brazil.

出版信息

Geroscience. 2017 Feb;39(1):51-59. doi: 10.1007/s11357-017-9957-y. Epub 2017 Jan 18.

Abstract

Growth hormone receptor knockout mice (GHRKO) are characterized by high insulin sensitivity and extended lifespan. Interestingly, the secretory activity of visceral fat in GHRKO mice is altered, stimulating whole body insulin sensitivity. In this study, we transplanted normal (N) mice with visceral fat pads from GHRKO or N mice to determine the role of visceral fat on the insulin signaling. We found that the transplant of visceral fat from GHRKO mice to N mice (N-GHRKO) improved whole body insulin sensitivity when comparing with sham-operated mice (N-S) and with mice that received visceral fat from N mice (N-N). This was associated with increased hepatic insulin sensitivity as observed by the increased phosphorylated insulin receptor and increased hepatic expression of Pparα and Pparγ. In conclusion, we demonstrated that visceral fat transplant from GHRKO mice into normal mice enhanced insulin sensitivity and glucose tolerance. These results further confirm the differential physiological role played by visceral adipose tissue from GH receptor deficient mice, indicating that the increase of this fat depot can be associated with beneficial effects on insulin signaling and longevity.

摘要

生长激素受体敲除小鼠(GHRKO)的特点是胰岛素敏感性高和寿命延长。有趣的是,GHRKO 小鼠内脏脂肪的分泌活性发生改变,刺激全身胰岛素敏感性。在这项研究中,我们将正常(N)小鼠的内脏脂肪垫移植到 GHRKO 或 N 小鼠中,以确定内脏脂肪对胰岛素信号的作用。我们发现,与假手术(N-S)和接受 N 小鼠内脏脂肪的小鼠(N-N)相比,将 GHRKO 小鼠的内脏脂肪移植到 N 小鼠(N-GHRKO)中可改善全身胰岛素敏感性。这与肝胰岛素敏感性增加有关,如磷酸化胰岛素受体增加和 Pparα 和 Pparγ 的肝表达增加所观察到的。总之,我们证明了将 GHRKO 小鼠的内脏脂肪移植到正常小鼠中可以增强胰岛素敏感性和葡萄糖耐量。这些结果进一步证实了生长激素受体缺失小鼠内脏脂肪组织发挥的不同生理作用,表明增加这种脂肪储存可能与胰岛素信号和长寿的有益作用相关。

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