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Sitagliptin Alleviates Obesity in Immature Mice by Inhibiting Oxidative Stress and Inflammation

  • Reproductive Biology: Original Article
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Abstract

To investigate the impact of Sitagliptin against obesity and the underlying mechanism. Obese immature mice were treated with 10, 30, and 90 mg/kg Sitagliptin, respectively. The body weights were recorded and the level of serum biochemical indexes were detected. The visceral fat ratio of each mouse was determined. The pathological change in adipose tissues was determined by HE staining, while F4/80 and CD206 levels in adipose tissues were determined by the immunohistochemical analysis. Lipid formation was evaluated by Oil red O staining assay. RAW264.7 cells were stimulated using oxLDL, followed by being incubated with different concentrations of Sitagliptin. The release of ADPN, IL-6, IL-1β, TNF-α, and the activity of SOD, was measured by ELISA assay. Western blotting was applied to determine adipsin, Nrf2, Keap1, and HO-1 protein levels. ROS level was checked using the DCFH-DA assay. RT-PCR assay was utilized to detect the mRNA levels of IL-6, IL-1β, TNF-α, Nrf2, Keap1, and HO-1. The body weight gain, infiltration of multinucleated cells, enlarged size of adipocytes, increased lipid accumulation, elevated visceral fat ratio, declined ADPN level, upregulated adipsin, and disordered serum biochemical indexes in obese immature mice were statistically significantly reversed by Sitagliptin. Excessive release of inflammatory factors and upregulated F4/80 and CD206 were observed in obese immature mice, which were statistically significantly repressed by Sitagliptin. Furthermore, the elevated MDA level, increased SOD activity, and inhibited Nrf2 pathway in obese immature mice were significantly reversed by Sitagliptin. In oxLDL stimulated RAW264.7 cells, increased release of inflammatory factors, ROS, and MDA, elevated SOD activity, and inactivated Nrf2 pathway were observed, which were statistically significantly abolished by the treatment of Sitagliptin. Sitagliptin alleviated obesity in immature mice by inhibiting inflammation and oxidative stress.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Pediatrics, The Second Affiliated Hospital (Jiande Branch), School of Medicine, Zhejiang University (The First People’s Hospital of Jiande), No. 599 Yanzhou Avenue, **n‘Anjiang Street, Jiande City, Hangzhou, Zhejiang, China

    **aoying Wang

  2. Department of Pediatrics, Sanitation Continuation School of Yuyao City, No. 139 West Shinan RoadZhejiang Province, Yuyao City, Ningbo City, China

    Wenbo Weng

  3. Department of Pharmacy, Children’s Hospital, Zhejiang University School of Medicine, No. 3333 Binsheng Road, Binjiang District, Hangzhou, 310052, Zhejiang, China

    Yifei Cui & Chaochun Zou

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  1. **aoying Wang
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Contributions

Chaochun Zou designed the research and wrote the original draft. **aoying Wang performed experiments. Wenbo Weng performed the analysis. Yifei Cui confirms the authenticity of all the raw data. All authors read and approved the final manuscript.

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Correspondence to Chaochun Zou.

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All animal experiments involved in this manuscript were authorized by the animal experimentation ethical committee of Zhejiang Yingyang Pharmaceutical Research and Development Co., LTD (Certificate No. ZJEY-20211118–02).

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Wang, X., Weng, W., Cui, Y. et al. Sitagliptin Alleviates Obesity in Immature Mice by Inhibiting Oxidative Stress and Inflammation. Reprod. Sci. (2024). https://doi.org/10.1007/s43032-024-01623-7

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