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

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Abstract

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.

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Acknowledgements

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.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Science, Alexandria University, Moharm Bek, 21511, Alexandria, Egypt

    Doaa A. Ghareeb

  2. Faculty of Science and Art, Department of Biology, King Khaled University, Besha, KSA, 3236, Saudi Arabia

    Hani S. Hafez

  3. Faculty of Pharmacy and drug manufacturing, Pharos University, Alexandria, Egypt

    Hend M. Hussien

  4. Faculty of Pharmacy, Alexandria University, El Khartoum Square, Azarita, 21521, Alexandria, Egypt

    Nihal F. Kabapy

  5. Department of Biology, Faculty of Science and Arts, Bisha, King Khaled University, 551, Bisha, Saudi Arabia

    Hani S. Hafez

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  1. Doaa A. Ghareeb
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Correspondence to Hani S. Hafez.

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Doaa A. Ghareeb and Hani S. Hafez contributed equally to this work

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Ghareeb, D.A., Hafez, H.S., Hussien, H.M. et al. Non-alcoholic fatty liver induces insulin resistance and metabolic disorders with development of brain damage and dysfunction. Metab Brain Dis 26, 253–267 (2011). https://doi.org/10.1007/s11011-011-9261-y

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