Peroxisome proliferator-activated receptors (PPARs)-independent functions of fish oil on glucose and lipid metabolism in diet-induced obese mice.
BACKGROUND
Fish oil is known to improve lifestyle-related diseases. These effects occur partly via activation of PPARs by the n-3 polyunsaturated fatty acids included abundantly in fish oil. We investigated fish oil functions on glucose and lipid metabolism that are both dependent on and independent of PPARs pathway.


METHODS
Mice were fed a diet containing 30 en% beef tallow (B diet) for twelve weeks to induce obesity. The mice were then divided into two groups which were fed either a B diet or a diet containing 30 en% fish oil (F diet). Each group was further divided into two groups which were administered PPARα and γ antagonists or vehicle once a day for three weeks.


RESULTS
The F diet groups showed lower triglyceride levels in plasma and liver than the B diet groups, but PPARs antagonists did not affect the triglyceride levels in either diet groups. The F diet groups also showed improvement of glucose tolerance compared with the B diet groups. However, PPARs antagonists made glucose tolerance worse in the F diet group but improved it in the B diet group. Therefore, by the administration of antagonists, glucose tolerance was inversely regulated between the B and F diets, and hypolipidemic action in the plasma and liver of the F diet group was not affected.


CONCLUSIONS
These results suggest that fish oil decreases lipid levels in plasma and liver via PPARs pathway-independent mechanism, and that glucose tolerance is inversely regulated by PPARs antagonists under diets containing different oils.
Wakutsu
Masaki
M
Department of Clinical Dietetics and Human Nutrition, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan.
Tsunoda
Nobuyo
N
Shiba
Sachiko
S
Muraki
Etsuko
E
Kasono
Keizo
K
D042962:Acyl-CoA Oxidase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D048429:Cell Size; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage* / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance / Q000097:blood / Q000178:diet therapy; D015228:Hypertriglyceridemia / Q000097:blood / Q000178:diet therapy; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000473:pathology; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D009765:Obesity / Q000097:blood / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D047493:PPAR alpha / Q000037:antagonists & inhibitors*; D047495:PPAR gamma / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism
D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D008055:Lipids; D047493:PPAR alpha; D047495:PPAR gamma; D012333:RNA, Messenger; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D042962:Acyl-CoA Oxidase; D064429:Fatty Acid Synthases; D005947:Glucose