Andrographolide modulates glucose metabolism in visceral adipose tissue in an Alzheimer's disease obese mouse model

Ormazabal, Paulina; Gherardelli, Camila; Pinto, Cristina; Servili, Evrim; Mendez-Orellana, Carolina; Wong, G. William; Contreras-Diaz, Roberto; Cisternas, Pedro; Inestrosa, Nibaldo C.

doi:https://doi.org/10.1016/j.jbc.2025.110607

Andrographolide modulates glucose metabolism in visceral adipose tissue in an Alzheimer's disease obese mouse model

Ormazabal, Paulina

[1];

Gherardelli, Camila

[2];

Pinto, Cristina

[3];

Servili, Evrim

[4];

Mendez-Orellana, Carolina

[2];

Wong, G. William

[5];

Contreras-Diaz, Roberto

[6];

Cisternas, Pedro

[7];

Inestrosa, Nibaldo C.

[3]

¹
Universidad San Sebastian
²
Pontificia Universidad Catolica de Chile
³
Escuela de Medicina
⁴
Universidad de Chile
⁵
Johns Hopkins University
⁶
Universidad de Atacama
⁷
Universidad de Las Americas - Chile

DOI

https://doi.org/10.1016/j.jbc.2025.110607

Date Issued

2025-10

Type

Artículo

Journal

Journal of Biological Chemistry

ISSN

1083-351X

Open Access

gold

Volume

301

Links

https://arca.umag.cl/handle/123456789/16006

Midlife obesity and high adiposity are recognized as risk factors for Alzheimer's disease (AD), with visceral adipose tissue (VAT) playing a central role due to its endocrine and metabolic activity. Disturbances in VAT metabolism and adipokine secretion exacerbate AD pathology. Andrographolide (Andro), known for its anti-diabetic properties, enhances neuronal glucose uptake and alleviates AD pathology. However, its effects on VAT metabolism in AD remain unexplored. This study aimed to investigate the impact of Andro on glucose metabolism in VAT using a high-fat diet (HFD)-induced obesity model in AD mice (APP/PS1). APP/PS1 mice were fed an HFD and received Andro injections (2 mg/kg, three times a week for 16 weeks). VAT samples were analyzed for glucose uptake, glycolytic rate, pentose phosphate flux, ADP-ATP levels, gene expression, and enzymatic activity of glucose metabolic regulators. In APP/PS1 mice, HFD significantly increased glucose uptake and reduced GLUT4 expression in VAT, effects counteracted by Andro (p < 0.05). Andro-treated HFD-fed mice exhibited reduced glucose oxidation through glycolysis (p < 0.05), leading to decreased ATP production (p < 0.05). Andro administration restored the activity of key glycolytic enzymes and mitigated several HFD-induced metabolic alterations (p < 0.05). The study reveals significant metabolic changes in the VAT of obese APP/PS1 mice and highlights Andro's potential as a therapeutic agent for addressing VAT impairment induced by obesity in AD.