Cross‐Organ Multi‐Omics Profiling of Systemic Alterations in 5xFAD Mice and Changes Associated with Huanglian Jiedu Decoction Treatment
- 1Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing China
- 2Beijing Academy of Traditional Chinese Medicine Beijing University of Chinese Medicine Beijing China
Abstract
Alzheimer's disease (AD) is increasingly recognized as a systemic disorder involving metabolic abnormalities beyond the brain, but links between hepatic alterations and neuroinflammation remain unclear. We integrated behavioral, histopathological, transcriptomic, proteomic, phosphoproteomic, and metabolomic analyses in male mice assigned to WT (n = 15), AD (n = 16), high‐dose HLJDD (n = 16), low‐dose HLJDD (n = 11), and donepezil (n = 10) groups and treated for 10 weeks. Longitudinal behavioral data were analyzed using repeated‐measures models, and omics p‐values were adjusted using the Benjamini–Hochberg FDR procedure. Cognitive impairment, glial activation, and neuroinflammation were accompanied by hepatic metabolic disturbances and alterations in insulin signaling and energy metabolism, implicating PPAR and PI3K/Akt‐related processes. HLJDD, particularly at the high dose, improved behavioral and neuropathological outcomes and shifted abnormalities in TCA‐cycle metabolites, amino acid neurotransmitters, and oxidative balance toward WT levels. To assess hepatocyte contributions to microglial inflammation, we established an AML12–BV2 conditioned‐medium model with hepatocyte PPAR‐γ knockdown. Conditioned medium from LPS/HLJDD‐cotreated AML12 cells elicited lower inflammatory responses in BV2 cells than medium from LPS‐treated hepatocytes. PPAR‐γ knockdown attenuated this effect, supporting a hepatocyte PPAR‐γ‐dependent contribution to microglial regulation and further investigation of hepatic involvement in HLJDD‐associated neuroprotection.
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BibTeX
@article{gao2026crossorgan,
title = {{Cross‐Organ Multi‐Omics Profiling of Systemic Alterations in 5xFAD Mice and Changes Associated with Huanglian Jiedu Decoction Treatment}},
author = {Wenya Gao and Jing Gao and Xiaohui Su and Xiangying Kong and Xiaolu Wei and Tunan Ding and Tiantian Guo and Shuangrong Gao and Yanyan Zhou and Junyi Zhou and Haiyu Zhao},
journal = {Advanced Science},
year = {2026},
month = oct,
doi = {10.1002/advs.78442},
url = {https://doi.org/10.1002/advs.78442},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Cross‐Organ Multi‐Omics Profiling of Systemic Alterations in 5xFAD Mice and Changes Associated with Huanglian Jiedu Decoction Treatment
AU - Wenya Gao
AU - Jing Gao
AU - Xiaohui Su
AU - Xiangying Kong
AU - Xiaolu Wei
AU - Tunan Ding
AU - Tiantian Guo
AU - Shuangrong Gao
AU - Yanyan Zhou
AU - Junyi Zhou
AU - Haiyu Zhao
PY - 2026
DA - 2026/10/31
JO - Advanced Science
DO - 10.1002/advs.78442
UR - https://doi.org/10.1002/advs.78442
AB - Alzheimer's disease (AD) is increasingly recognized as a systemic disorder involving metabolic abnormalities beyond the brain, but links between hepatic alterations and neuroinflammation remain unclear. We integrated behavioral, histopathological, transcriptomic, proteomic, phosphoproteomic, and metabolomic analyses in male mice assigned to WT (n = 15), AD (n = 16), high‐dose HLJDD (n = 16), low‐dose HLJDD (n = 11), and donepezil (n = 10) groups and treated for 10 weeks. Longitudinal behavioral data were analyzed using repeated‐measures models, and omics p‐values were adjusted using the Benjamini–Hochberg FDR procedure. Cognitive impairment, glial activation, and neuroinflammation were accompanied by hepatic metabolic disturbances and alterations in insulin signaling and energy metabolism, implicating PPAR and PI3K/Akt‐related processes. HLJDD, particularly at the high dose, improved behavioral and neuropathological outcomes and shifted abnormalities in TCA‐cycle metabolites, amino acid neurotransmitters, and oxidative balance toward WT levels. To assess hepatocyte contributions to microglial inflammation, we established an AML12–BV2 conditioned‐medium model with hepatocyte PPAR‐γ knockdown. Conditioned medium from LPS/HLJDD‐cotreated AML12 cells elicited lower inflammatory responses in BV2 cells than medium from LPS‐treated hepatocytes. PPAR‐γ knockdown attenuated this effect, supporting a hepatocyte PPAR‐γ‐dependent contribution to microglial regulation and further investigation of hepatic involvement in HLJDD‐associated neuroprotection.
SN - 2198-3844
ER -