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Updated: Aug 24, 2025
Determination of Fatty Acid Oxidation and Lipogenesis in Mouse Primary Hepatocytes
Published on: August 27, 2015
Visualization and quantification of de novo lipogenesis using a FASN-2A-GLuc mouse model
Wenjiao Li1, Song Zhang1,2, Xin Fu1
1State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Medical University of PLA, Xi'an, China.
Background:
De novo lipogenesis (DNL) is a dynamic process that converts excess carbohydrates into fatty acids to maintain cellular homeostasis. Dysregulation of DNL is associated with diverse obesity-related diseases and many tumor types. Therefore, monitoring DNL in real-time with high sensitivity should be highly beneficial when screening therapeutic agents for their potential use as obesity treatments.
Methods:
A sequence coding for Gaussia luciferase (GLuc) preceded by a 2A peptide was inserted into the murine fatty acid synthase (FASN) genetic locus by homologous recombination to generate FASN-2A-GLuc mice. The luciferase mouse model was evaluated in conditions of physical and pharmacological stimuli by in vivo and ex vivo imaging.
Results:
The distribution of bioluminescence signals in different organs was identical to the FASN expression: high in white fat, brown fat, and the lungs. In addition, the bioluminescence signals accurately recapitulated the dynamic change of FASN in response to fasting and refeeding conditions. Moreover, with this murine reporter model, we also discovered that fatostatin, a synthetic inhibitor of sterol regulatory element-binding proteins, effectively inhibited DNL in multiple organs, especially in adipose tissues under a high-carbohydrate diet.
Conclusions:
Our FASN-2A-GLuc reporter mouse model proved to be a sensitive visualization tool for monitoring both systemic and organ-specific DNL in real time.
