Inhibition of fatty acid synthase prevents preadipocyte differentiation

Bernhard Schmid1, Jörg F Rippmann, Moh Tadayyon

  • 1Department of Metabolic Diseases, Boehringer Ingelheim Pharma GmbH and Co KG, 88397 Biberach an der Riss, Germany. Bernhard.Schmid@bc.boehringer-ingelheim.com

Insights

Inhibiting fatty acid synthase (FAS) prevents lipid accumulation in differentiating fat cells. This suggests FAS is crucial for supporting preadipocyte differentiation and lipid droplet formation.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Metabolism

Background:

  • Fatty acid synthase (FAS) plays a role in fatty acid synthesis.
  • Adipose tissue expresses FAS, indicating a potential role in adipocyte function.
  • Previous studies show FAS inhibition reduces food intake in rodents.

Purpose of the Study:

  • To investigate the effect of reduced FAS activity on adipocyte differentiation.
  • To determine if FAS is essential for preadipocyte differentiation.

Main Methods:

  • 3T3-L1 cells were used to model adipocyte differentiation.
  • FAS activity was suppressed using pharmacological inhibitors (cerulenin, triclosan, C75) and siRNA.
  • Lipid droplet accumulation was measured via visual inspection and [1-(14C)]acetate incorporation.
  • Gene expression of FAS, CEBPalpha, PPARgamma, and CD36 was analyzed using RT-PCR.

Main Results:

  • Pharmacological inhibition and siRNA suppression of FAS dramatically reduced lipid droplet accumulation in differentiating 3T3-L1 cells.
  • FAS inhibition significantly decreased the mRNA levels of key adipogenic transcription factors (CEBPalpha, PPARgamma) and CD36.
  • FAS activity was essential for lipid synthesis, with acetate incorporation reduced by up to 90%.

Conclusions:

  • FAS activity is essential for supporting preadipocyte differentiation.
  • FAS-generated signals appear to be critical for the accumulation of lipids and the expression of differentiation markers in adipocytes.