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Article

Role of the mTOR‑FOXO1 pathway in obesity‑associated renal tubulointerstitial inflammation

  • Authors:
    • Hong Sun
    • Xinyu Shao
    • Jiajia He
    • Michal Golos
    • Bimin Shi
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Oncology, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Changzhou, Jiangsu 213000, P.R. China, Centre for Amyloidosis and Acute Phase Protein, Division of Medicine, University College London (UCL), London NW3 2PF, UK
  • Pages: 1284-1293
    |
    Published online on: December 5, 2018
       https://doi.org/10.3892/mmr.2018.9727
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Abstract

Since obesity is largely responsible for the growing incidence of renal tubulointerstitial inflammation, exploration into the mechanisms of obesity‑associated tubulointerstitial inflammation is essential. Studies have demonstrated that mammalian target of rapamycin (mTOR) is a crucial molecule in the pathogenesis of renal inflammation, including regulating the expression of inflammatory factors. The purpose of the present study was to further elucidate the role of mTOR in obesity‑associated tubulointerstitial inflammation. In the clinical study, obese and healthy subjects were recruited for physical examination, as well as the collection of blood and urine samples. Further study was performed on a high fat diet (HFD)‑induced obese rat model and a cultured human renal tubular epithelial cell line (HK‑2). The clinical study demonstrated that the participants with obesity had increased serum lipids, creatinine (Cr), urinary albumin to creatinine ratio (UACR) and urinary neutrophil gelatinase‑associated lipocalin (u‑NGAL). Moreover, the level of urinary monocyte chemoattractant protein‑1 (u‑MCP‑1) was increased in the participants with obesity, and it was positively correlated with free fatty acid (FFA), UACR and u‑NGAL. In the in vivo study, the results indicated that the levels of serum lipids, Cr and blood urea nitrogen (BUN), as well as 24 h urine protein and u‑NGAL, were significantly increased in the HFD‑fed obese rats. In addition, the infiltration of CD68+ cells into the renal interstitial area and the release of interleukin‑1β (IL‑1β) was observed in the kidneys of obese rats. Meanwhile, the supernatant from HK‑2 cells treated with palmitic acid stimulated THP‑1 monocyte migration. The upregulation of MCP‑1, phosphorylated forkhead boxO1 (p‑FOXO1), and phosphorylated mTOR (p‑mTOR) was observed in vivo and in vitro. However, inhibition of mTOR was able to alleviate the above effects. Overall, these results demonstrated that activated mTOR induced FOXO1 phosphorylation, which mediates renal MCP‑1 release, causes tubulointerstitial inflammation and ultimately leads to pathological renal changes and dysfunction. However, inhibition of mTOR may play a renoprotective role during the progression of obesity‑associated tubulointerstitial inflammation.
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Copy and paste a formatted citation
Spandidos Publications style
Sun H, Shao X, He J, Golos M and Shi B: Role of the mTOR‑FOXO1 pathway in obesity‑associated renal tubulointerstitial inflammation. Mol Med Rep 19: 1284-1293, 2019.
APA
Sun, H., Shao, X., He, J., Golos, M., & Shi, B. (2019). Role of the mTOR‑FOXO1 pathway in obesity‑associated renal tubulointerstitial inflammation. Molecular Medicine Reports, 19, 1284-1293. https://doi.org/10.3892/mmr.2018.9727
MLA
Sun, H., Shao, X., He, J., Golos, M., Shi, B."Role of the mTOR‑FOXO1 pathway in obesity‑associated renal tubulointerstitial inflammation". Molecular Medicine Reports 19.2 (2019): 1284-1293.
Chicago
Sun, H., Shao, X., He, J., Golos, M., Shi, B."Role of the mTOR‑FOXO1 pathway in obesity‑associated renal tubulointerstitial inflammation". Molecular Medicine Reports 19, no. 2 (2019): 1284-1293. https://doi.org/10.3892/mmr.2018.9727
Copy and paste a formatted citation
x
Spandidos Publications style
Sun H, Shao X, He J, Golos M and Shi B: Role of the mTOR‑FOXO1 pathway in obesity‑associated renal tubulointerstitial inflammation. Mol Med Rep 19: 1284-1293, 2019.
APA
Sun, H., Shao, X., He, J., Golos, M., & Shi, B. (2019). Role of the mTOR‑FOXO1 pathway in obesity‑associated renal tubulointerstitial inflammation. Molecular Medicine Reports, 19, 1284-1293. https://doi.org/10.3892/mmr.2018.9727
MLA
Sun, H., Shao, X., He, J., Golos, M., Shi, B."Role of the mTOR‑FOXO1 pathway in obesity‑associated renal tubulointerstitial inflammation". Molecular Medicine Reports 19.2 (2019): 1284-1293.
Chicago
Sun, H., Shao, X., He, J., Golos, M., Shi, B."Role of the mTOR‑FOXO1 pathway in obesity‑associated renal tubulointerstitial inflammation". Molecular Medicine Reports 19, no. 2 (2019): 1284-1293. https://doi.org/10.3892/mmr.2018.9727
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