Abstract
HIGH CHOLESTEROL DIET (HCD) INDUCES NON-ALCOHOLIC FATTY LIVER (NAFLD) IN ZEBRAFISH

Clifton Justin David* and T. J. Pandian

ABSTRACT

Obesity leads to non-alcoholic fatty liver disease (NAFLD), where fat gets deposited in hepatocytes; progressgradually into non-alcoholic steato-hepatitis (NASH) and Hepato-Cellular Carcinoma (HCC). Treatment of NAFLD is expensive owing to non-availability of biomarkers and therapeutic targets for detection and treatment. Objective:We aim to generate NAFLD zebrafish model by High Cholesterol Diet (HCD) and analysehistologically the effects of HCD in NAFLD and NASH induction. Methods: Zebrafish were fed HCD (6- 8%) for weeks (8-16 weeks) for inducing NAFLD and confirmed by morphological and histological analyses of liver. Results:Feeding HCD for 16 weeks induced symptoms of NAFLD, confirmed by fatty liver morphology, significantly (P<0.05) increased hepato-somatic index (HSI; 0.659 ± 0.0545) and histological analyses of liver sections showed degenerated hepatocytes, dense accumulation of LDs and hepatic membrane dis-integrity confirming its progression into NASH after 18 weeks while, controls fed with regular diet had less LDs and remained healthy. Conclusion: we show that zebrafish can be used as aNAFLD model using less expensive HCD feeding displaying symptoms as in humans. Identification of novel therapeutic targets and biomarkers in NAFLD may helpearly diagnostics and personalized therapeutics in humans. Advantages and disadvantages of using zebrafish model to investigate NAFLD are discussed.

Keywords: high-cholesterol diet, NAFLD, NASH, fatty liver, hepato-somatic index, zebrafish.


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