Inhibition of fatty acid synthase prevents preadipocyte differentiation

• Published in: Biochemical and biophysical research communications Vol. 328; no. 4; pp. 1073 - 1082
• Main Authors: Schmid, Bernhard, Rippmann, Jörg F., Tadayyon, Moh, Hamilton, Bradford S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.03.2005
• Subjects: 3T3-L1; 3T3-L1 Cells; 4-Butyrolactone - analogs & derivatives; 4-Butyrolactone - pharmacology; Adipocyte; Adipocytes - cytology; Adipocytes - drug effects; Adipocytes - enzymology; Animals; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cerulenin - pharmacology; Differentiation; Fatty acid synthase; Fatty Acid Synthases - antagonists & inhibitors; Fatty Acid Synthases - genetics; Fatty Acid Synthases - metabolism; Gene Silencing; Mice; Triclosan - pharmacology; Adipocyte; Fatty acid synthase; Differentiation; 3T3-L1
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2005.01.067

Inhibition of fatty acid synthase (FAS) reduces food intake in rodents. As adipose tissue expresses FAS, we sought to investigate the effect of reduced FAS activity on adipocyte differentiation. FAS activity was suppressed either pharmacologically or by siRNA during differentiation of 3T3-L1 cells. Cerulenin (10 μM), triclosan (50 μM), and C75 (50 μM) reduced dramatically visible lipid droplet accumulation, while incorporation of [1- 14C]acetate into lipids was reduced by 75%, 70%, and 90%, respectively. Additionally, the substances reduced FAS, CEBPα, and PPARγ mRNA by up to 85% compared to that of control differentiated cells. Transient transfection with FAS siRNA suppressed FAS mRNA and FAS activity, and this was accompanied by reduction of CEBPα and PPARγ mRNA levels, and complete prevention of lipid accumulation. CD36, a late marker of differentiation, was also reduced. Together, these results suggest that FAS generated signals may be essential to support preadipocyte differentiation.