Treatment with omega-3 fatty acids but not exendin-4 improves hepatic steatosis.
BACKGROUND
Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in the Western world. The aim of this study was to evaluate the biochemical and histological effects of omega-3 fatty acid and exendin-4 treatment on NAFLD in an animal model.


METHODS
Sixty-three 8-week-old outbred Sprague-Dawley male rats were used for this study. Three animals were used as procedure controls, and 30 rats were fed a methionine and choline deficient (MCD) diet and 30 were fed a regular chow diet. In each group of 30 animals, 10 served as controls, 10 received exendin-4, and 10 received omega-3 fatty acids. After 75 days of treatment, the animals were euthanized, the tissues and serum were harvested, and the livers were formalin-fixed for histology.


RESULTS
The MCD diet was exceptionally efficient at producing fatty livers. The MCD control animals had a liver steatosis score of 38+/-6.7 (of 50 possible); treatment with exendin-4 was not associated with a significant reduction of steatosis (44+/-5.16, P=0.07) and the omega-3 fatty acid treatment was associated with a significant decrease in the liver steatosis score (15.6+/-13.46, P<0.001) compared with both the controls and the exendin-4 groups. The omega-3 fatty acid treatment increased serum aspartate aminotransferase significantly, whereas exendin-4 had no effect.


CONCLUSIONS
In an animal model of NAFLD, the omega-3 fatty acid therapy was associated with significant improvement in hepatic steatosis compared with exendin-4. These data suggest that omega-3 fatty acid supplements may have a potential therapeutic role in patients with NAFLD.
Bulchandani
Deepti G
DG
Division of Endocrinology, University of Kansas School of Medicine, Kansas City, Missouri 64108, USA.
Nachnani
Jagdish S
JS
Nookala
Anupama
A
Naumovitch
Christina
C
Herndon
Betty
B
Molteni
Agostino
A
Quinn
Tim
T
Alba
Laura M
LM
D054392:Adipokines / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003314:Corn Oil / Q000494:pharmacology; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D042926:Cytochrome P-450 CYP4A / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D000077270:Exenatide; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005234:Fatty Liver / Q000188:drug therapy* / Q000378:metabolism; D005395:Fish Oils / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014688:Venoms / Q000494:pharmacology*
D054392:Adipokines; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D003314:Corn Oil; D000077270:Exenatide; D019392:Cytochrome P-450 CYP2E1; D042926:Cytochrome P-450 CYP4A