Metabolic Brain Disease

, 26:253 | Cite as

Non-alcoholic fatty liver induces insulin resistance and metabolic disorders with development of brain damage and dysfunction

  • Doaa A. Ghareeb
  • Hani S. Hafez
  • Hend M. Hussien
  • Nihal F. Kabapy
Original Paper


In the present study we investigated the effect of the non-alcoholic fatty liver disease (NAFLD) on the alterations in the activity of neurotransmitters catabolizing enzymes and energy catabolising enzymes, prooxidants, endogenous antioxidants and proinflammatory cytokines in brain tissue of NAFLD rats. Rats were intraperitonealy injected with CCl4 solution at a dose of (0.021 mole/Kg, 20 μL, body weight) three times weekly for four weeks. Acetylcholine esterase (AChE), monoamine oxidase (MAO), prooxidant/ antioxidants status, ATPase, lipid profile and glucose level were estimated spectrophotometrically while inflammatory markers; interleukin 6 and tumor necrosis factor alpha (IL6 and TNF-α) and insulin were assessed by ELISA technique. Our results showed that the induced NAFLD and insulin resistance (IR) were accompanied with hyperglycemia and hyperlipidemia and lowered brain glucose level with elevated ATPase activity, prooxidant status (TBARS level, xanthine oxidase and cytochrome 2E1 activities), and inflammatory markers. Through the induction period AChE activity was significantly increased compared to control in blood, liver and brain tissues. Also, MAO activity was significantly increased in both brain and liver tissue but decreased in serum compared with control. These biochemical data were supported with pathophysiological analysis that showed severe neurodegeneration, pyknosis acuolations and cavitations. These observations warrant the reassessment of the conventional concept that the NAFLD with IR progression may induce disturbances in activities of neurotransmitters catabolising enzymes and energy production accompanied with oxidative stress and metabolic disorders, acting as relative risk factors for brain dysfunction and damage with the development of age-associated neurodegenerative diseases such as Alzheimer's disease.


NAFLD Insulin resistance Brain dysfunction AChE MAO 



Special thanks for Prof Dr. Ashraf A. Khalil, protein technology department, the city of scientific research and Application technology, who gave us several advises through the work design.

Competing interests

There is neither financial competing interest (political, personal, religious, ideological, academic, intellectual, commercial or any other) to declare in relation to this manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Doaa A. Ghareeb
    • 1
  • Hani S. Hafez
    • 2
    • 5
  • Hend M. Hussien
    • 3
  • Nihal F. Kabapy
    • 4
  1. 1.Department of Biochemistry, Faculty of ScienceAlexandria UniversityAlexandriaEgypt
  2. 2.Faculty of Science and Art, Department of BiologyKing Khaled UniversityBeshaSaudi Arabia
  3. 3.Faculty of Pharmacy and drug manufacturingPharos UniversityAlexandriaEgypt
  4. 4.Faculty of PharmacyAlexandria UniversityAlexandriaEgypt
  5. 5.Department of Biology, Faculty of Science and Arts, BishaKing Khaled UniversityBishaSaudi Arabia

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