Selenite supplementation modulates the hepatic metabolic sensors AMPK and SIRT1 in binge drinking exposed adolescent rats by avoiding oxidative stress

Food Funct. 2021 Apr 7;12(7):3022-3032. doi: 10.1039/d0fo02831b. Epub 2021 Mar 12.

Abstract

Binge drinking (BD) is the main alcohol consumption pattern among teenagers. Recently, oxidative stress (OS) generated by BD exposure has been related to hepatic metabolic deregulation and cardiovascular dysfunction. This study analyzed if BD by generating oxidative stress modulates the alteration in hepatic energy homeostasis through two important regulators of energy metabolism: the NAD+-dependent sirtuin deacetylase (SIRT1) and AMP-activated protein kinase (AMPK) and if supplementation with the antioxidant selenium (Se) improves these metabolic disorders. Four groups of adolescent rats supplemented or not with Se (0.4 ppm) and exposed to intermittent i.p. BD were used. BD rats showed an increased AST/ALT ratio, total bilirubin in serum and lipid peroxidation in the liver. The BD rats also showed a higher abdominal/thoracic ratio and increased levels of TG, gluc, and chol compared to the control group, provoking an increase in mean blood pressure (MBP). This alcohol consumption pattern decreased hepatic Se deposits, cytoplasmic GPx activity, and GSH levels as well as the expressions of two metabolic sensors and the pAMPK/AMPK ratio. Se supplementation restored antioxidant parameters and decreased lipid oxidation, avoiding OS and improving the hepatic expression of pAMPK and SIRT1, contributing to the improvement of metabolic (better lipid profile and IRS-1 expression) and vascular function (lower MBP), and to the increase of hepatic functionality (lower AST/ALT ratio). All these actions decrease cardiometabolic risk factor development in the short and long term and could disrupt the relationship between BD and MS, two problems which are currently affecting adolescents.

MeSH terms

  • AMP-Activated Protein Kinases / drug effects
  • AMP-Activated Protein Kinases / metabolism
  • Adolescent
  • Adolescent Behavior*
  • Animals
  • Antioxidants / administration & dosage*
  • Antioxidants / pharmacology
  • Binge Drinking*
  • Dietary Supplements
  • Humans
  • Liver / metabolism
  • Male
  • Models, Animal
  • Oxidative Stress
  • Rats
  • Rats, Wistar
  • Selenious Acid / administration & dosage*
  • Selenious Acid / pharmacology
  • Sirtuin 1 / drug effects
  • Sirtuin 1 / metabolism

Substances

  • Antioxidants
  • AMP-Activated Protein Kinases
  • Sirtuin 1
  • Selenious Acid