A low fish oil inhibits SREBP-1 proteolytic cascade, while a high-fish-oil feeding decreases SREBP-1 mRNA in mice liver: relationship to anti-obesity

• Main Authors: Teruyo Nakatani, Hyoun-Ju Kim, Yasushi Kaburagi, Kazuki Yasuda, Osamu Ezaki
• Format: Article
• Language: English
• Published: Elsevier 2003-02-01
• Series: Journal of Lipid Research
• Subjects: n-3 fatty acids; dual-energy X-ray absorptiometry; stearoyl-CoA desaturase; fatty acid synthase; acetyl-CoA carboxylase; acyl-CoA oxidase
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520312244

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 α (PPARα). 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 PPARα 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 PPARα rather than SREBP-1 decrease might be related to the antiobesity effect of fish oil feeding.