Dietary supplementation with fish oil alters the expression levels of proteins governing mitochondrial dynamics and prevents high-fat diet-induced endothelial dysfunction.
Diets supplemented with fish oil (FO), which is rich in n-3 PUFA, have been shown to modify several key risk factors for CVD. The purpose of the present study was to determine the effect of FO supplementation on mitochondrial dynamic protein expression in the endothelium and on endothelial cell function. Male apoE-deficient (apoE-/-) mice (8 weeks old, n 12 per group) were fed a high-fat diet containing 45% fat (HFD group) or a HFD with partial replacement of lard with 10% (w/w) FO (FO group) (total EPA and DHA content 64.1 g/kg) for 8 weeks. ApoE-/- mice in the FO group had a greater endothelium-dependent vasorelaxation response to acetylcholine (Ach) than those in the HFD group. The atherosclerotic lesion volume in the aortic sinus of mice in the FO group was 54% lower than that in the HFD group (P< 0.01). In addition, the aortas isolated from mice in the FO group had higher expression levels of Mfn2 and Opa1 but lower expression levels of Fis1 than those from the HFD group. Compared with mice fed the HFD, those fed the FO diet showed significantly lower levels of mitochondrial oxidative stress, cytochrome c release and caspase-3 activity (each P< 0.05). Furthermore, FO-fed mice displayed increased NO release and availability and enhanced endothelial NO synthase activity compared with HFD-fed mice. Taken together, these results reveal a novel mechanism by which FO protects against endothelial cell dysfunction, which may result in improved mitochondrial dynamics.
Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University (Northern Campus),Guangzhou,Guangdong Province,People's Republic of China.
Ruifang
R
Sun
Department of Nutrition,School of Public Health, Sun Yat-sen University (Northern Campus),Guangzhou,Guangdong Province,People's Republic of China.
Xiaoming
X
Wang
Department of Nutrition,School of Public Health, Sun Yat-sen University (Northern Campus),Guangzhou,Guangdong Province,People's Republic of China.
Yan
Y
Liu
Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University (Northern Campus),Guangzhou,Guangdong Province,People's Republic of China.
Min
M
Xia
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D059305:Diet, High-Fat / Q000009:adverse effects; D019587:Dietary Supplements; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use; D005395:Fish Oils / Q000627:therapeutic use*; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D011897:Random Allocation; D013047:Specific Pathogen-Free Organisms; D014664:Vasodilation
D001057:Apolipoproteins E; C561064:FIS1 protein, mouse; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C488751:Mfn2 protein, mouse; C498809:Opa1 protein, mouse