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

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 high-fat diet, female APP mice had higher adiposity, insulin resistance, and mitochondrial dysfunction (hypothalamus)

SUBMITTER: Allerton TD 

PROVIDER: S-EPMC11525932 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature