Title:Liver-Brain Axis in Sporadic Alzheimer’s Disease: Role of Ten Signature Genes in a Mouse Model
Volume: 20
Issue: 9
Author(s): Ruchi Jakhmola-Mani, Anam Islam and Deepshikha Pande Katare*
Affiliation:
- Proteomics and Translational Research Lab, Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida 201313,India
Keywords:
Liver-brain axis, NAFLD, Alzheimer's disease, DEGs, gene interaction networks, TUBB5.
Abstract:
Aim: Poor nutritional effect of junk food induces injuries to the liver and the brain but
still most of the developing nations survive on these diets to compensate for the fast-paced
lifestyle. The aim of the study is to infer the protein-connections behind the liver-brain axis and
identify the role of these proteins in causing neurodegenerative disorders.
Background: Chronic consumption of fructose and fat-rich food works as a toxin in the body and
has the ability to cause a negative metabolic shift. Recently a study was published in Annals of Internal
Medicine (2019) citing the loss of vision and hearing in a 14-year-old boy whose diet was
strictly restricted to fries and junk-food for almost a decade. This puts the entire body on insulin resistance
and related co-morbidities and causes simultaneous damaging effects on the liver as well
as the brain. This work provides insights into the liver-brain axis and explains how the liver is involved
in brain related disorders.
Objective: In this study, transcriptomic data related to chronic eating of junk-food was analyzed
and simultaneous damage that happens in the liver and the brain was assessed at the molecular
level.
Methods: Transcriptomic study was taken from the GEO database and analysed to find out the
genes dysregulated in both the liver and the brain during this metabolic stress. Cytoscapev3.7 was
used to decipher the signalling between the liver and the brain. This connection between both is
called as the liver-brain axis.
Result: The results obtained from our study indicate the role of TUBB5-HYOU1-SDF2L1-DECR1-
CDH1-EGFR-SKP2-SOD1-IRAK1-FOXO1 gene signature in the decline of concurrent liver
and brain health. Dysregulated levels of these genes are linked to molecular processes like cellular
senescence, hypoxia, glutathione synthesis, amino acid modification, increased nitrogen content,
synthesis of BCAAs, cholesterol biosynthesis, steroid hormone signalling and VEGF pathway.
Conclusion: We strongly advocate that prolonged consumption of junk food is a major culprit in
brain related disorders like Alzheimer’s disease and propose that receptors for brain diseases lie outside
the brain and aiming them for drug discovery and design may be beneficial in future clinical
studies. This study also discusses the connection between NAFLD (non-alcoholic fatty liver disease)
and sAD (sporadic Alzheimer’s disease) owing to liver-brain axis.
