Cafeteria Diet Feeding in Young Rats Leads to Hepatic Steatosis and Increased Gluconeogenesis under Fatty Acids and Glucagon Influence

Nutrients. 2018 Oct 23;10(11):1571. doi: 10.3390/nu10111571.

Abstract

Gluconeogenesis overstimulation due to hepatic insulin resistance is the best-known mechanism behind elevated glycemia in obese subjects with hepatic steatosis. This suggests that glucose production in fatty livers may differ from that of healthy livers, also in response to other gluconeogenic determinant factors, such as the type of substrate and modulators. Thus, the aim of this study was to investigate the effects of these factors on hepatic gluconeogenesis in cafeteria diet-induced obese adult rats submitted to a cafeteria diet at a young age. The livers of the cafeteria group exhibited higher gluconeogenesis rates when glycerol was the substrate, but lower rates were found when lactate and pyruvate were the substrates. Stearate or glucagon caused higher stimulations in gluconeogenesis in cafeteria group livers, irrespective of the gluconeogenic substrates. An increased mitochondrial NADH/NAD⁺ ratio and a reduced rate of 14CO₂ production from [14C] fatty acids suggested restriction of the citric acid cycle. The higher glycogen and lipid levels were possibly the cause for the reduced cellular and vascular spaces found in cafeteria group livers, likely contributing to oxygen consumption restriction. In conclusion, specific substrates and gluconeogenic modulators contribute to a higher stimulation of gluconeogenesis in livers from the cafeteria group.

Keywords: NAFLD; glucose production; hemodynamic changes; high caloric density food; hyperglycemia; obesity.

MeSH terms

  • Animals
  • Diet / adverse effects*
  • Energy Intake
  • Fatty Acids / metabolism*
  • Fatty Liver / chemically induced*
  • Feeding Behavior
  • Glucagon / metabolism*
  • Gluconeogenesis / drug effects*
  • Glucose / metabolism
  • Lactic Acid / administration & dosage
  • Lactic Acid / pharmacology
  • Male
  • Obesity / chemically induced
  • Oxygen Consumption
  • Pyruvic Acid / administration & dosage
  • Pyruvic Acid / pharmacology
  • Rats
  • Rats, Wistar

Substances

  • Fatty Acids
  • Lactic Acid
  • Pyruvic Acid
  • Glucagon
  • Glucose