Time-dependent changes and association between liver free fatty acids, serum lipid profile and histological features in mice model of nonalcoholic fatty liver disease.
OBJECTIVE
Methionine-choline deficient (MCD) diet duration necessary for development of non-alcoholic fatty liver disease (NAFLD) and the dynamic of lipid profile and fatty acids are not completely established. The study examined dynamics and association between liver free fatty acids (FFA), serum lipid profile and liver morphological changes on MCD diet-induced NAFLD in mice.


METHODS
Male C57BL/6 mice (n = 28) were divided into four groups (n = 7 per group): control: fed with standard chow, MCD diet-fed groups: 2, 4 or 6 weeks. After treatment, liver and blood samples were taken for histopathology, serum lipid profile, and liver FFA composition.


RESULTS
Hepatic FFA profile showed a decrease in saturated acids, arachidonic and docosahexaenoic acid, whereas proportions of docosapentaenoic, oleic and linoleic acid were increased. Total cholesterol, HDL and triglycerides progressively decreased, whereas LDL level progressively increased. Focal fatty change in the liver appeared after 2 weeks, whereas diffuse fatty change with severe inflammation and ballooned hepatocytes were evident after 6 weeks.


CONCLUSIONS
Six-week diet model may be appropriate for investigation of the role of lipotoxicity in the progression of NAFLD. Therefore, supplementation with n-3 polyunsaturated acid like DHA, rather than DPA, especially in the initial stage of fatty liver disease, may potentially have preventive effects and alleviate development of NAFLD/NASH and may also potentially reduce cardiovascular risk by moderating dyslipidemia.
Faculty of Medicine, Institute of Pathophysiology "Ljubodrag Buba Mihailović", University of Belgrade, Belgrade, Serbia.
Milena N
MN
Stanković
Faculty of Medicine, Institute of Pathophysiology "Ljubodrag Buba Mihailović", University of Belgrade, Belgrade, Serbia.
Dušan R
DR
Mladenović
Department of Bromatology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Ivana
I
Duričić
Department of Bromatology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Slađana S
SS
Šobajić
Department of Bromatology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Jasmina
J
Timić
Faculty of Medicine, Institute of Pathophysiology "Ljubodrag Buba Mihailović", University of Belgrade, Belgrade, Serbia.
Bojan
B
Jorgačević
Faculty of Medicine, Institute of Pathophysiology "Ljubodrag Buba Mihailović", University of Belgrade, Belgrade, Serbia.
Vuk
V
Aleksić
Faculty of Medicine, Institute of Pathophysiology "Ljubodrag Buba Mihailović", University of Belgrade, Belgrade, Serbia.
Danijela B
DB
Vučević
Institute of Digestive Diseases, Clinical Centre of Serbia, Belgrade, Serbia.
Rada
R
Ješić-Vukićević
Faculty of Medicine, Institute of Pathophysiology "Ljubodrag Buba Mihailović", University of Belgrade, Belgrade, Serbia. Electronic address: tanjamm@med.bg.ac.rs.
Tatjana S
TS
Radosavljević
D000818:Animals; D002794:Choline / Q000008:administration & dosage; D004032:Diet; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008055:Lipids / Q000097:blood*; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008715:Methionine / Q000172:deficiency; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D012307:Risk Factors; D013997:Time Factors
D005230:Fatty Acids, Nonesterified; D008055:Lipids; D008715:Methionine; D002794:Choline
Free fatty acids; Lipid status; Methionine-choline deficient diet; Mice; NAFLD