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Journal of Lipid Research, Vol. 44, 369-379, February 2003
Copyright © 2003 by Lipid Research, Inc.
* Division of Clinical Nutrition, National Institute of Health and Nutrition, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8636, Japan
Division of Community Health, Research Institute, International Medical Center of Japan, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
Department of Metabolic Disorder, Research Institute, International Medical Center of Japan, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
1 To whom correspondence should be addressed. e-mail: ezaki{at}nih.go.jp
Rodents fed fish oil showed less obesity with a reduction of triglyceride synthesis in liver, relative to other dietary oils, along with a decrease of mature form of sterol regulatory element binding protein-1 (SREBP-1) and activation of peroxisome proliferator-activated receptor 
(PPAR). 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 antiobesity effect, mice were fed fish oil in a range from 10 to 60 energy percent (en%). Fish oil feeding decreased body weight and fat mass in a dose-dependent manner, in parallel with PPAR 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 lipogenic genes, 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 its pharmacological doses, and that activation of PPAR rather than SREBP-1 decrease might be related to the antiobesity effect of fish oil feeding.
Abbreviations: ACC, acetyl-CoA carboxylase; ACO, acyl-CoA oxidase; ACS, acyl-CoA synthetase; DEXA, dual-energy X-ray absorptiometry; DHA, docosahexaenoic acid; en%, energy percent; EPA, eicosapentaenoic acid; FAS, fatty acid synthase; MCAD, medium-chain acyl-CoA dehydrogenase; PLSD, protected least significant difference; PPAR, peroxisome proliferator-activated receptor; PSL, phosphostimulated luminescence; S1P, Site-1 protease; SCAP, SREBP cleavage-activating protein; SCD, stearoyl-CoA desaturase; SRE, sterol regulatory element; SREBP, sterol regulatory element binding protein; UCP, uncoupling protein; WAT, white adipose tissue
Supplementary key words n-3 fatty acids • dual-energy X-ray absorptiometry • stearoyl-CoA desaturase • fatty acid synthase • acetyl-CoA carboxylase • acyl-CoA oxidase • medium-chain acyl-CoA dehydrogenase • uncoupling protein • lipoprotein lipase • sterol regulatory element binding protein-1
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