Abstract
Purpose
Hypertension is one of the major risk factors for renal failure and cardiovascular diseases, and is caused by various abnormalities including the contractility of blood vessels. Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which mimic human type 2 diabetes, are frequently used to study obesity-induced insulin resistance (IR) and hypertension. Human omentin-1 is one of the recently identified adipocytokines. We previously demonstrated that human omentin-1 not only caused vasodilation in rat isolated blood vessels, but also prevented inflammatory responses, a possible mechanism relating IR, in human vascular endothelial cells. Taken together, we hypothesized that human omentin-1 may reduce obesity-induced IR and hypertension in OLETF rats.
Methods
OLETF rats were intraperitoneally administered with human omentin-1 for 7 days.
Results
Human omentin-1 had no influence on overweight, hyperglycemia, urinary glucose extraction, hyperinsulinemia, and systemic IR in OLETF rats. Human omentin-1 decreased systolic blood pressure in OLETF rats. The measurement of isometric contraction revealed that human omentin-1 had no influence on the agonist-induced contractile and relaxant responses in isolated thoracic aorta from OLETF rats. However, the relaxant response mediated by human insulin was converted into the contractile response in thoracic aorta from OLETF rats, which was prevented by human omentin-1. The Western blotting revealed that human omentin-1 improved the decrease in endothelial nitric oxide synthase activation in isolated thoracic aorta from OLETF rats.
Conclusion
In summary, we for the first time revealed that human omentin-1 partly reduces vascular IR and thereby inhibits hypertension in OLETF rats.
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Data availability
The data that support the findings of this study are available on request from the corresponding author.
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Acknowledgements
We appreciate Kitasato University Veterinary Teaching Hospital for lending the Echo system.
Funding
This study was supported by a Kitasato University Research Grant (to HY).
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Contributions
Conceptualization: YO, TK, KO, MO, and HY.
Investigation: YO, KA, RN, KO, and MO.
Resources: KO, MO, and HY.
Data curation: YO, KA, RN, and HY.
Writing-original draft preparation: YO.
Writing review and editing: HY.
Visualization: YO and HY.
Supervision: TK, KO, MO, and HY.
Project administration: KO, MO, and HY.
Funding acquisition: HY.
All authors have read and agreed to the published version of the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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An animal study was approved by the ethical committee of School of Veterinary Medicine, the Kitasato University (approval no. 21–066), and was performed in conformity with an institutional guideline of the Kitasato University.
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Okamura, Y., Adachi, K., Niijima, R. et al. Human omentin-1 reduces vascular insulin resistance and hypertension in Otsuka Long-Evans Tokushima Fatty rats. Naunyn-Schmiedeberg's Arch Pharmacol 397, 3379–3387 (2024). https://doi.org/10.1007/s00210-023-02795-w
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DOI: https://doi.org/10.1007/s00210-023-02795-w