Fructose-Rich Diet Affects Mitochondrial DNA Damage and Repair in Rats.
Evidence indicates that many forms of fructose-induced metabolic disturbance are associated with oxidative stress and mitochondrial dysfunction. Mitochondria are prominent targets of oxidative damage; however, it is not clear whether mitochondrial DNA (mtDNA) damage and/or its lack of repair are events involved in metabolic disease resulting from a fructose-rich diet. In the present study, we evaluated the degree of oxidative damage to liver mtDNA and its repair, in addition to the state of oxidative stress and antioxidant defense in the liver of rats fed a high-fructose diet. We used male rats feeding on a high-fructose or control diet for eight weeks. Our results showed an increase in mtDNA damage in the liver of rats fed a high-fructose diet and this damage, as evaluated by the expression of DNA polymerase γ, was not repaired; in addition, the mtDNA copy number was found to be significantly reduced. A reduction in the mtDNA copy number is indicative of impaired mitochondrial biogenesis, as is the finding of a reduction in the expression of genes involved in mitochondrial biogenesis. In conclusion, a fructose-rich diet leads to mitochondrial and mtDNA damage, which consequently may have a role in liver dysfunction and metabolic diseases.
Department of Science and Technology, University of Sannio, 82100 Benevento, Italy. federica.cioffi@unisannio.it.
Federica
F
Cioffi
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Naples II, 81100 Caserta, Italy. pasquale.lasala@gmail.com.
Rosalba
R
Senese
Department of Science and Technology, University of Sannio, 82100 Benevento, Italy. rosalba.senese@unina2.it.
Pasquale
P
Lasala
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Naples II, 81100 Caserta, Italy. angela.ziello@gmail.com.
Angela
A
Ziello
Department of Biology, University of Naples "Federico II", 80100 Napoli, Italy. antonia.lanni@unina2.it.
Arianna
A
Mazzoli
Department of Biology, University of Naples "Federico II", 80100 Napoli, Italy. arimazzoli@hotmail.it.
Raffaella
R
Crescenzo
Department of Biology, University of Naples "Federico II", 80100 Napoli, Italy. rcrescen@unina.it.
Giovanna
G
Liverini
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Naples II, 81100 Caserta, Italy. liverini@unina.it.
Antonia
A
Lanni
Department of Science and Technology, University of Sannio, 82100 Benevento, Italy. goglia@unisannio.it.
Fernando
F
Goglia
Department of Biology, University of Naples "Federico II", 80100 Napoli, Italy. susiossa@unina.it.
Susanna
S
Iossa
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056915:DNA Copy Number Variations / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D004272:DNA, Mitochondrial / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D004032:Diet; D005632:Fructose / Q000008:administration & dosage* / Q000009:adverse effects*; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004272:DNA, Mitochondrial; D012333:RNA, Messenger; D005632:Fructose; D000080242:8-Hydroxy-2'-Deoxyguanosine; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003849:Deoxyguanosine
fructose-rich diet; mitochondrial DNA (mtDNA); mitochondrial biogenesis; oxidative damage; repair mechanisms