Effect of Initial Aging and High-Fat/High-Fructose Diet on Mitochondrial Bioenergetics and Oxidative Status in Rat Brain

  • Raffaella Crescenzo
  • Maria Stefania Spagnuolo
  • Rosa Cancelliere
  • Lucia Iannotta
  • Arianna Mazzoli
  • Cristina Gatto
  • Susanna IossaEmail author
  • Luisa Cigliano


Middle age is an early stage of the aging process, during which the consumption of diets rich in saturated fats and/or simple sugars might influence brain function, but only few data are available on this issue. We therefore investigated the impact of a diet rich in saturated fat and fructose (HFF) on mitochondrial physiology in hippocampus and frontal cortex of middle-aged rats (1 year old), by including a group of adult rats (90 days) as a “negative control,” lacking the putative effect of aging. Middle-aged rats were fed HFF or control diet for 4 weeks. Mitochondrial function was analyzed by high-resolution respirometry and by assessing the amount of respiratory complexes. Markers of oxidative balance, as well as the protein content of uncoupling protein 2 (UCP2), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and peroxisome proliferator-activated receptor alpha (PPARα), were also assessed. A decrease in the activity of complex I was detected in both brain areas of middle-aged rats. In hippocampus, mitochondrial respiratory capacity and complex IV content decreased with age and increased with HFF diet. Higher protein oxidative damage, decreased antioxidant defenses, and increased UCP2 and PGC-1α content were found in hippocampus of middle-aged rats. HFF feeding induced a significant reduction in the amount of UCP2, PGC-1α, and PPARα, together with higher protein oxidative damage, in both brain areas. Overall, our results point to middle age as a condition of early brain aging for mitochondrial function, with hippocampus being an area more susceptible to metabolic impairment than frontal cortex.


Mitochondria Western diet Hippocampus Cortex Fructose Middle age 



The authors wish to thank Dr. Emilia de Santis for skillful management of animal house.

Funding Information

This work was supported by a grant from University of Naples Federico II - Ricerca Dip 2017 and by a FIRB - Futuro in Ricerca grant (RBFR12QW4I_004) from the Italian Ministry of Education, University and Research (MIUR).

Compliance with Ethical Standards

Treatment, housing, and euthanasia of animals met the guidelines set by the Italian Health Ministry. All experimental procedures involving animals were approved by “Comitato Etico-Scientifico per la Sperimentazione Animale” of the University of Naples Federico II.

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12035_2019_1617_Fig9_ESM.png (142 kb)
Supplementary Figure 9

Representative traces of oxygen flux in the hippocampus of middle-aged rats. (PNG 1.71 mb)

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High resolution image (TIFF 1.71 mb)
12035_2019_1617_Fig10_ESM.png (138 kb)
Supplementary Figure 10

Representative western blot of respiratory complexes I-V carried out on protein extracts from hippocampus of adult (1) middle-aged (2) and middle-aged HFF (3) rats. (PNG 12.9  mb)

12035_2019_1617_MOESM2_ESM.tiff (12.9 mb)
High resolution image (TIFF 12.9 mb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of BiologyUniversity of Naples Federico II, Complesso Universitario Monte S. AngeloNaplesItaly
  2. 2.Department of Bio-Agrofood Science, Institute for the Animal Production System in Mediterranean EnvironmentNational Research Council (CNR-ISPAAM)NaplesItaly

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