Nitric oxide donors rescue metabolic and mitochondrial dysfunction in obese Alzheimer's model

Authors

• Timothy D. Allerton, Pennington Biomedical Research Center, Baton Rouge, LA
• James E. Stampley, Louisiana State University, Baton Rouge, LA
• Zhen Li, Cedars-Sinai Medical Center, Los Angeles, CA
• Xiaoman Yu, Cedars-Sinai Medical Center, Los Angeles, CA
• Heather Quiariate, Pennington Biomedical Research Center, Baton Rouge, LA
• Jake E. Doiron, Pennington Biomedical Research Center, Baton Rouge, LA
• Ginger White, Louisiana State University, Baton Rouge, LA
• Zach Wigger, Pennington Biomedical Research Center, Baton Rouge, LA
• Manas Ranjan Gartia, Louisiana State University, Baton Rouge, LA
• David J. Lefer, Cedars-Sinai Medical Center, Los Angeles, CA
• Paul Soto, Louisiana State University, Baton Rouge, LA
• Brian A. Irving, Louisiana State University, Baton Rouge, LA

Document Type

Article

Publication Date

10-30-2024

Publication Title

Scientific Reports

Abstract

Reduced nitric oxide (NO) bioavailability is a pathological link between obesity and Alzheimer’s disease (AD). Obesity-associated metabolic and mitochondrial bioenergetic dysfunction are key drivers of AD pathology. The hypothalamus is a critical brain region during the development of obesity and dysfunction is an area implicated in the development of AD. NO is an essential mediator of blood flow and mitochondrial bioenergetic function, but the role of NO in obesity-AD is not entirely clear. We investigated diet-induced obesity in female APPswe/PS1dE9 (APP) mouse model of AD, which we treated with two different NO donors (sodium nitrite or L-citrulline). After 26 weeks of a highfat diet, female APP mice had higher adiposity, insulin resistance, and mitochondrial dysfunction (hypothalamus) than non-transgenic littermate (wild type) controls. Treatment with either sodium nitrite or L-citrulline did not reduce adiposity but improved whole-body energy expenditure, substrate oxidation, and insulin sensitivity. Notably, both NO donors restored hypothalamic mitochondrial respiration in APP mice. Our findings suggest that NO is an essential mediator of whole-body metabolism and hypothalamic mitochondrial function, which are severely impacted by the dual insults of obesity and AD pathology

First Page

1*

Last Page

8

DOI

10.1038/s41598-024-75870-8

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Recommended Citation

Allerton, Timothy D.; Stampley, James E.; Li, Zhen; Yu, Xiaoman; Quiariate, Heather; Doiron, Jake E.; White, Ginger; Wigger, Zach; Gartia, Manas Ranjan; Lefer, David J.; Soto, Paul; and Irving, Brian A., "Nitric oxide donors rescue metabolic and mitochondrial dysfunction in obese Alzheimer's model" (2024). LSU-LCMC Cancer Center Faculty Publications. 213.
https://digitalscholar.lsuhsc.edu/llcc_facpubs/213
10.1038/s41598-024-75870-8