Research Article: Alogliptin improves survival and health of mice on a high‐fat diet

Date Published: January 15, 2019

Publisher: John Wiley and Sons Inc.

Author(s): Biao Zhu, Yixiang Li, Lingwei Xiang, Jiajia Zhang, Li Wang, Bei Guo, Minglu Liang, Long Chen, Lin Xiang, Jing Dong, Min Liu, Wen Mei, Huan Li, Guangda Xiang.

http://doi.org/10.1111/acel.12883

Abstract

Alogliptin is a commonly prescribed drug treating patients with type 2 diabetes. Here, we show that long‐term intervention with alogliptin (0.03% w/w in diet) improves survival and health of mice on a high‐fat diet. Alogliptin intervention takes beneficial effects associated with longevity, including increased insulin sensitivity, attenuated functionality decline, decreased organ pathology, preserved mitochondrial function, and reduced oxidative stress. Autophagy activation is proposed as an underlying mechanism of these beneficial effects. We conclude that alogliptin intervention could be considered as a potential strategy for extending lifespan and healthspan in obesity and overweight.

Partial Text

The number of overweight and obese individuals worldwide has increased dramatically over the past 30 years, leading to an explosion of obesity‐related health problems associated with increased morbidity and mortality. Patients with obesity exhibit many manifestations of accelerated aging, such as cardiovascular disease, diabetes, hypertension, dyslipidemia, nonalcoholic fatty liver disease and inflammatory disorders, all of which reduce lifespan. For these reasons, ways to improve the obesity‐related health problems for extending longevity are actively pursued.

Our present data for the first time suggested that alogliptin intervention extends longevity and improves health of mice with excess caloric intake. These beneficial effects are mainly related to increased insulin sensitivity, attenuated function decline, decreased organ pathology, inhibited inflammation, preserved mitochondrial function, and reduced oxidative stress. Autophagy activation may be involved in these beneficial effects. Thus, alogliptin intervention is considered as a potential strategy for extending lifespan and healthspan in obesity and overweight.

More detailed methods are described in the Supporting Information Appendix S1.

The authors declare no competing financial interests.

B.Z., H.L., J.Z., B.G., L.W., M.L., and L.C. conducted the animal experiments. Y.L., L.X., J.D., and M.L. performed the in vitro experiments. B.Z., L.X., W.M., H.L., and B.G. analyzed the data and wrote the manuscript. G.X. is the guarantor of this work and, as such, has full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

 

Source:

http://doi.org/10.1111/acel.12883

 

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