Folic acid supplementation attenuates high fat diet induced hepatic oxidative stress via regulation of NADPH oxidase.
Diets high in saturated fat and cholesterol facilitate weight gain, a predisposing factor that contributes to the onset of obesity and metabolic disorders. Hepatic oxidative stress is commonly reported in various animal models of obesity and has been associated with enhanced expression of NADPH oxidase. We have previously reported several antioxidant mechanisms through which folic acid confers protection during hyperhomocysteinemia-induced oxidative stress. The objective of the present study was to investigate whether folic acid supplementation ameliorates high-fat diet induced oxidative stress in the liver, and to identify the underlying mechanisms. Male C57BL/6J mice were fed a control diet, a high-fat diet, or a high-fat diet supplemented with folic acid for 12 weeks. A high-fat diet led to increased body mass, hepatic lipid peroxidation, and liver injury. There was a significant increase in hepatic NADPH oxidase activity, which was associated with enhanced expression of several NADPH-oxidase subunits. Folic acid supplementation had a protective effect against high-fat diet induced hepatic oxidative stress and liver injury. Further analysis revealed that the antioxidant effect of folic acid was attributed, in part, to transcriptional regulation of NADPH oxidase. These results suggested that folic acid supplementation may be hepatoprotective from liver injury associated with a high-fat diet.
Integrative Biology Laboratory, Canadian Centre for Agri-food Research in Health and Medicine, St. Boniface Hospital Research Centre, 351 Tache Avenue, Winnipeg, MB R2H 2A6, Canada.
Lindsei K
LK
Sarna
Nan
N
Wu
Pengqi
P
Wang
Sun-Young
SY
Hwang
Yaw L
YL
Siow
Karmin
K
O
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D019610:Cytoprotection; D059305:Diet, High-Fat / Q000009:adverse effects*; D019587:Dietary Supplements; D015536:Down-Regulation; D005492:Folic Acid / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010750:Phosphoproteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015430:Weight Gain
D000975:Antioxidants; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D010750:Phosphoproteins; D012333:RNA, Messenger; C079789:neutrophil cytosol factor 67K; D005492:Folic Acid; D002374:Catalase; D013482:Superoxide Dismutase; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D005978:Glutathione