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. 2023 Mar;201(3):1344-1357. doi: 10.1007/s12011-022-03247-x. Epub 2022 May 2.

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.

Keywords: AMPK; Autophagy; Non-alcoholic fatty liver disease; SIRT-1; Selenium-enriched probiotic.

MeSH terms

  • AMP-Activated Protein Kinases
  • Animals
  • Autophagy
  • Diet, High-Fat / adverse effects
  • Diet, Western / adverse effects
  • Fructose / pharmacology
  • Lipid Metabolism
  • Liver / metabolism
  • Male
  • Non-alcoholic Fatty Liver Disease* / drug therapy
  • Non-alcoholic Fatty Liver Disease* / metabolism
  • Probiotics* / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Selenium* / metabolism

Substances

  • Selenium
  • AMP-Activated Protein Kinases
  • Fructose