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Nutrients. 2019 Apr 8;11(4). pii: E799. doi: 10.3390/nu11040799.

Fatty Acid Desaturase Involvement in Non-Alcoholic Fatty Liver Disease Rat Models: Oxidative Stress Versus Metalloproteinases.

Author information

1
Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy. giuseppina.palladini@unipv.it.
2
Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy. giuseppina.palladini@unipv.it.
3
Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy. lauragiuseppin.dipasqua01@universitadipavia.it.
4
Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy. clarissa.berardo01@universitadipavia.it.
5
Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy. veronica.siciliano01@universitadipavia.it.
6
Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy. plinio.richelmi@unipv.it.
7
Centro Grandi Strumenti, University of Pavia, 27100 Pavia, Italy. barbara.mannucci@unipv.it.
8
Institute of Molecular Genetics, Italian National Research Council (CNR), 27100 Pavia, Italy. leta@igm.cnr.it.
9
Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy. v.rizzo@smatteo.pv.it.
10
Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy. v.rizzo@smatteo.pv.it.
11
Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy. stefano.perlini@unipv.it.
12
Emergency Department, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy. stefano.perlini@unipv.it.
13
Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy. mariapia.vairetti@unipv.it.
14
Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy. andrea.ferrigno@unipv.it.

Abstract

We investigated changes in fatty acid desaturases, D5D, D6D, D9-16D and D9-18D, and their relationship with oxidative stress, matrix metalloproteinases (MMPs) and serum TNF-alpha in two rat models of non-alcoholic fatty liver disease NAFLD. Eight-week-old male Wistar rats fed for 3 weeks with methionine-choline⁻deficient (MCD) diet and eleven-week-old Obese male Zucker rats were used. Serum levels of hepatic enzymes and TNF-alpha were quantified. Hepatic oxidative stress (ROS, TBARS and GSH content) and MMP-2 and MMP-9 (protein expression and activity) were evaluated. Liver fatty acid profiling, performed by GC-MS, was used for the quantification of desaturase activities. Higher D5D and D9-16D were found in Obese Zucker rats as well as an increase in D9-18D in MCD rats. D6D was found only in MCD rats. A negative correlation between D5D and D9-16D versus TBARS, ROS and TNF-alpha and a positive correlation with GSH were shown in fatty livers besides a positive correlation between D9-18D versus TBARS, ROS and TNF-alpha and a negative correlation with GSH. A positive correlation between D5D or D9-16D or D9-18D versus protein expression and the activity of MMP-2 were found. NAFLD animal models showed comparable serum enzymes. These results reinforce and extend findings on the identification of therapeutic targets able to counteract NAFLD disorder.

KEYWORDS:

TNF-alpha; desaturase; fatty liver; metalloproteinases; oxidative stress

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