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Selenium-Enriched Probiotic Alleviates Western Diet-Induced Non-alcoholic Fatty Liver Disease in Rats via Modulation of Autophagy Through AMPK/SIRT-1 Pathway

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Abstract

Current study was aimed to investigate the ability of L.acidophilus SNZ 86 to biotransform inorganic selenium to a more active organic form, resulting in trace element enrichment. Selenium-enriched L. acidophilus SNZ 86 has been shown to be effective in the treatment of a variety of gastrointestinal illnesses, indicating the need for additional research to determine the full potential of this therapeutic strategy in the treatment of metabolic disorders. Herein, we employed the western style diet-induced model of non-alcoholic fatty liver disease (NAFLD) to explore the therapeutic effect of selenium-enriched probiotic (SP). Male Sprague Dawley rats (160–180 g) were fed a high-fat (58% Kcal of fat) and high-fructose (30% w/v) diet for 12 weeks to develop an animal model mimicking NAFLD. High-fat and High-fructose diet-fed rats exhibited hyperglycemia, hyperlipidemia, insulin resistance, abnormal liver function test, increased hepatic oxidative stress, and steatosis. SP was then administered orally (L acidophilus 1 × 109 CFU/ml containing 0.4 g Se/day; p.o.) for 8 weeks. The selenium enrichment within L. acidophilus SNZ 86 was validated by TEM, which allowed for visualisation of the selenium deposition and size distribution in the probiotic. In NAFLD control rats, the expression of autophagy proteins (LC-3 A/B and Beclin), AMPK, and SIRT-1 was significantly reduced indicating downregulation of autophagy. However, supplementation of SP ameliorates hepatic steatosis as evidenced by improved biochemical markers and autophagic activation via upregulation of the AMPK and SIRT-1 pathway showing the relevance of autophagy in the disease aetiology. Collectively, these findings provide us with a better understanding of the role of SP in the treatment of hepatic steatosis and establish a therapeutic basis for potential clinical application of SP in the prevention of NAFLD and associated pathological conditions.

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Funding

This study is funded by the National Institute of Pharmaceutical Education and Research.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Laboratory of Epigenetics and Diseases, National Institute of Pharmaceutical Education and Research, S.A.S Nagar (Mohali), Punjab, 160062, Mohali, India

    Rajat Pant, Nisha Sharma, Shaheen Wasil Kabeer, Shivam Sharma & Kulbhushan Tikoo

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  2. Nisha Sharma
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  3. Shaheen Wasil Kabeer
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Contributions

RP and KT designed the research work and wrote the manuscript; RP, NS, SKW, and SS performed the experiments and analysed and compiled the data; KT supervised and edited the final manuscript.

Corresponding author

Correspondence to Kulbhushan Tikoo.

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All institutional and national guidelines for the care and use of laboratory animals were followed. The animal studies were approved by the animal ethics committee of the NIPER S.A.S Nagar (IAEC18/09).

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Pant, R., Sharma, N., Kabeer, S.W. et al. Selenium-Enriched Probiotic Alleviates Western Diet-Induced Non-alcoholic Fatty Liver Disease in Rats via Modulation of Autophagy Through AMPK/SIRT-1 Pathway. Biol Trace Elem Res 201, 1344–1357 (2023). https://doi.org/10.1007/s12011-022-03247-x

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