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Papers In Press, published online ahead of print November 16, 2002
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Division of Clinical Nutrition, National Institute of Health and Nutrition, Tokyo 162-8636
Corresponding Author: ezaki{at}nih.go.jp
Fish oil feeding showed less obesity in rodents with a reduction of triglyceride synthesis in liver, relative to other dietary oils. These effects are associated with alterations of two transcription factors in liver; decrease of mature form of sterol regulatory element-binding protein-1 (SREBP-1) to reduce lipid synthesis and activation of peroxisome proliferator-activator receptor a (PPARa) to enhance fatty acid b oxidation. Decrease of mature SREBP-1 protein by fish oil feeding was due to either inhibition of SREBP-1 proteolytic cascade or to decrease of its mRNA. To clarify its mechanism and relation to inhibitory effects of obesity, mice were fed fish oil in a range from 10 to 60 energy percent (en%) and liver SREBP-1 protein and mRNA levels were measured and their contribution to obesity was elucidated. Fish oil feeding decreased body weight and fat mass in a dose-dependent manner, in parallel with PPARa activation and a decrease of SREBP-1 mRNA. However, compared with 0 en% fish oil feeding, 10 en% fish oil feeding decreased mature SREBP-1 protein by 50% with concomitant decreases of its target genes such as fatty acid synthase, acetyl-CoA carboxylase, and stearoyl-CoA desaturase-1, while precursor SREBP-1 protein rather increased by 1.3-fold. These data suggest that physiological doses of fish oil feeding effectively decrease expression of liver lipogenic enzymes by inhibiting SREBP-1 proteolytic cascade, while substantial decrease of SREBP-1 expression is observed in pharmacological doses of fish oil feeding, and that activation of PPARa rather than SREBP-1 decrease might be related to the anti-obesity effects of fish oil feeding.
Revised on October 15, 2002
Accepted on November 13, 2002
A low fish oil feeding inhibits SREBP-1 proteolytic cascade, while a high fish oil feeding decreases SREBP-1 mRNA in mice liver: its relationship to anti-obesity effect
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