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脂肪细胞特异性孤雌霉素受体敲除小鼠中,脂肪组织功能障碍独立于肥胖发生。

Adipose Tissue Dysfunction Occurs Independently of Obesity in Adipocyte-Specific Oncostatin Receptor Knockout Mice.

机构信息

Adipocyte Biology Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.

Matrix Biology Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.

出版信息

Obesity (Silver Spring). 2018 Sep;26(9):1439-1447. doi: 10.1002/oby.22254.

DOI:10.1002/oby.22254
PMID:30226002
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6146404/
Abstract

OBJECTIVE

This study examined the phenotypic effects of adipocyte-specific oncostatin M receptor (OSMR) loss in chow-fed mice.

METHODS

Chow-fed adipocyte-specific OSMR knockout (FKO) mice and littermate OSMR controls were studied. Tissue weights, insulin sensitivity, adipokine production, and stromal cell immunophenotypes were assessed in epididymal fat (eWAT); serum adipokine production was also assessed. In vitro, adipocytes were treated with oncostatin M, and adipokine gene expression was assessed.

RESULTS

Body weights, fasting blood glucose levels, and eWAT weights did not differ between genotypes. However, the eWAT of OSMR mice was modestly less responsive to insulin stimulation than that of OSMR mice. Notably, significant increases in adipokines, including C-reactive protein, lipocalin 2, intercellular adhesion molecule-1, and insulinlike growth factor binding protein 6, were observed in the eWAT of OSMR mice. In addition, significant increases in fetuin A and intercellular adhesion molecule-1 were detected in OSMR serum. Flow cytometry revealed a significant increase in leukocyte number and modest, but not statistically significant, increases in B cells and T cells in the eWAT of OSMR mice.

CONCLUSIONS

The chow-fed OSMR mice exhibited adipose tissue dysfunction and increased proinflammatory adipokine production. These results suggest that intact adipocyte oncostatin M-OSMR signaling is necessary for adipose tissue immune cell homeostasis.

摘要

目的

本研究旨在探讨脂肪细胞特异性生长分化因子 11(OSMR)缺失对食用标准饲料的小鼠表型的影响。

方法

研究了食用标准饲料的脂肪细胞特异性 OSMR 敲除(FKO)小鼠及其同窝对照 OSMR 小鼠。检测附睾脂肪(eWAT)中的组织重量、胰岛素敏感性、脂肪因子产生和基质细胞免疫表型;检测血清脂肪因子的产生。在体外,用生长分化因子 11 处理脂肪细胞,检测脂肪因子基因的表达。

结果

两组小鼠的体重、空腹血糖水平和 eWAT 重量无差异。然而,OSMR 小鼠的 eWAT 对胰岛素刺激的反应性略低于 OSMR 小鼠。值得注意的是,OSMR 小鼠的 eWAT 中多种脂肪因子(包括 C 反应蛋白、脂联素 2、细胞间黏附分子 1 和胰岛素样生长因子结合蛋白 6)显著增加。此外,OSMR 血清中的胎球蛋白 A 和细胞间黏附分子 1 也显著增加。流式细胞术显示,OSMR 小鼠的 eWAT 中白细胞数量显著增加,B 细胞和 T 细胞略有增加,但无统计学意义。

结论

食用标准饲料的 OSMR 小鼠表现出脂肪组织功能障碍和促炎脂肪因子产生增加。这些结果表明,完整的脂肪细胞生长分化因子 11-OSMR 信号通路对于脂肪组织免疫细胞的稳态是必要的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2aa/6146404/f3d7455bc699/nihms976281f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2aa/6146404/f35852828baf/nihms976281f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2aa/6146404/a5dc88c3a097/nihms976281f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2aa/6146404/1f28992ba7e4/nihms976281f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2aa/6146404/4d8a2a1c64b1/nihms976281f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2aa/6146404/058793147cbd/nihms976281f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2aa/6146404/f3d7455bc699/nihms976281f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2aa/6146404/f35852828baf/nihms976281f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2aa/6146404/a5dc88c3a097/nihms976281f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2aa/6146404/1f28992ba7e4/nihms976281f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2aa/6146404/4d8a2a1c64b1/nihms976281f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2aa/6146404/058793147cbd/nihms976281f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2aa/6146404/f3d7455bc699/nihms976281f6.jpg

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