Differentiated Hepatic Response to Fructose Intake during Adolescence Reveals the Increased Susceptibility to Non-Alcoholic Fatty Liver Disease of Maternal High-Fat Diet Male Rat Offspring

Mol Nutr Food Res. 2020 Feb;64(3):e1900838. doi: 10.1002/mnfr.201900838. Epub 2020 Jan 16.

Abstract

Scope: Non-alcoholic fatty liver disease (NAFLD) among adolescents has been related to fructose intake. Additionally, maternal high-fat diet (mHFD) increases the offspring susceptibility to NAFLD at adulthood. Here, it is hypothesized that mHFD may exacerbate the fructose impact in adolescent male rat offspring, by changing the response of contributing mechanisms to liver injury.

Methods and results: Female Wistar rats receive standard (mSTD: 9% fat) or high-fat diet (mHFD: 29% fat) prior mating throughout pregnancy and lactation. After weaning, offspring receive standard chow and, from the 25th to 45th day, receive water or fructose-drinking water (15%). At 46 days old, fructose groups show increased adiposity, increased serum and hepatic triglycerides, regardless of maternal diet. Fructose aggravates the hepatic imbalance of redox state already exhibited by mHFD offspring. The hepatic activation of cellular repair pathways by fructose, such as unfolded protein response and macroautophagy, is disrupted only in mHFD offspring. Fructose does not change the liver morphology of mSTD offspring. However, it intensifies the liver injury already present in mHFD offspring.

Conclusion: Fructose intake during adolescence accelerates the emergence of NAFLD observed previously at the adult life of mHFD offspring, and reveals a differentiated hepatic response to metabolic insult, depending on the maternal diet.

Keywords: adolescence; fructose intake; hepatic lipid metabolism; maternal high-fat diet; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animals
  • Autophagy
  • Body Weight
  • Diet, High-Fat*
  • Disease Susceptibility
  • Endoplasmic Reticulum Stress
  • Female
  • Fructose / toxicity*
  • Male
  • Maternal Nutritional Physiological Phenomena
  • Non-alcoholic Fatty Liver Disease / etiology*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Oxidative Stress
  • Pregnancy
  • Rats, Wistar
  • Triglycerides / blood
  • Unfolded Protein Response

Substances

  • Triglycerides
  • Fructose