Increased hepatic de novo lipogenesis and mitochondrial efficiency in a model of obesity induced by diets rich in fructose

Eur J Nutr. 2013 Mar;52(2):537-45. doi: 10.1007/s00394-012-0356-y. Epub 2012 Apr 28.

Abstract

Purpose: To assess hepatic de novo lipogenesis and mitochondrial energetics as well as whole-body energy homeostasis in sedentary rats fed a fructose-rich diet.

Methods: Male rats of 90 days of age were fed a high-fructose or control diet for 8 weeks. Body composition, energy balance, oxygen consumption, carbon dioxide production, non-protein respiratory quotient, de novo lipogenesis and insulin resistance were measured. Determination of specific activity of hepatic enzymes of de novo lipogenesis, mitochondrial mass, oxidative capacity and degree of coupling, together with parameters of oxidative stress and antioxidant defence, was also carried out.

Results: Body energy and lipid content as well as plasma insulin and non-esterified fatty acids were significantly higher in fructose-fed than in control rats. Significantly higher rates of net de novo lipogenesis and activities of hepatic lipogenic enzymes fatty acid synthase and stearoyl CoA desaturase-1 were found in fructose-fed rats compared to controls. Mitochondrial protein mass and degree of coupling were significantly higher in fructose-fed rats compared to controls. Hepatic mitochondria showed oxidative damage, both in the lipid and in the protein component, together with decreased activity of antioxidant defence.

Conclusion: Liver mitochondrial compartment is highly affected by fructose feeding. The increased mitochondrial efficiency allows liver cells to burn less substrates to produce ATP for de novo lipogenesis and gluconeogenesis. In addition, increased lipogenesis gives rise to whole body and ectopic lipid deposition, and higher mitochondrial coupling causes mitochondrial oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aconitate Hydratase / metabolism
  • Animals
  • Antioxidants / metabolism
  • Blood Glucose / analysis
  • Body Composition / drug effects
  • Disease Models, Animal
  • Energy Metabolism / drug effects
  • Fatty Acids, Nonesterified / blood
  • Fructose / administration & dosage*
  • Insulin / blood
  • Insulin Resistance
  • Lipid Peroxidation / drug effects
  • Lipids / blood
  • Lipogenesis*
  • Liver / metabolism*
  • Male
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / metabolism
  • Obesity / metabolism*
  • Obesity / physiopathology
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Stearoyl-CoA Desaturase / metabolism
  • Superoxide Dismutase / metabolism

Substances

  • Antioxidants
  • Blood Glucose
  • Fatty Acids, Nonesterified
  • Insulin
  • Lipids
  • Mitochondrial Proteins
  • Fructose
  • Stearoyl-CoA Desaturase
  • Superoxide Dismutase
  • Aconitate Hydratase