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The effect of leptin on ulcerative colitis (UC) has been controversial. The present study aimed to investigate the role of leptin and its receptor ob‑R in UC and the underlying mechanism of this role. The level of serum leptin and the protein expression of the leptin receptor ob‑R in the colonic mucosa were determined in patients with UC. Experimental colitis was induced through intrarectal administration of 2,4,6‑trinitrobenzene sulfonic acid (TNBS) in leptin receptor‑deficient Zucker rats (LR‑D). The body weight, disease activity index, colon length, and macroscopic and histopathological appearance were evaluated. Furthermore, the myeloperoxidase (MPO) enzyme activity and cytokine levels in colon tissues were also determined. The expression of the signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3 (p‑STAT3), nuclear factor (NF)‑κBp65, and Ras homolog gene family member A (RhoA) proteins in colon tissues was assessed. The results revealed that the expression of the leptin receptor ob‑R was increased in the colonic mucosa but the serum leptin level was not altered in patients with UC compared with healthy volunteers. The severity of experimental colitis, represented by body weight loss, disease activity index, colon length, and macroscopic and histological changes, was ameliorated in LR‑D rats compared with the wild‑type (WT) rats. Moreover, the MPO activity; levels of cytokines including interleukin (IL)‑1β, IL‑6, and tumor necrosis factor‑α; and expression of p‑STAT3, NF‑κB, and RhoA proteins were reduced in colon tissues of LR‑D rats compared with WT rats. In conclusion, activation of the leptin receptor ob‑R is an important pathogenic mechanism of UC, and leptin receptor deficiency may provide resistance against TNBS‑induced colitis by inhibiting the NF‑κB and RhoA signaling pathways.


Yan-Ming Tian, Si-Yu Tian, Dong Wang, Fang Cui, Xiang-Jian Zhang, Yi Zhang. Elevated expression of the leptin receptor ob‑R may contribute to inflammation in patients with ulcerative colitis. Molecular medicine reports. 2019 Nov;20(5):4706-4712

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PMID: 31702041

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