Dietary Fat Content Influences PanIN Progression and Pancreatic Cancer Development in Mice

Area of Science:

• Oncology
• Metabolism
• Cancer Biology

Background:

• Dietary macronutrient composition influences pancreatic cancer.
• The effect of ketogenic diets (KD) on early pancreatic cancer is unclear.

Purpose of the Study:

• Investigate how dietary lipids affect Kras-driven pancreatic neoplasia initiation and progression.
• Examine effects of low-fat diet (LFD), high-fat diet (HFD), and KD in a mouse model.

Main Methods:

• Utilized Ptf1aCreERT2;KrasG12V mouse model.
• Administered LFD, HFD, and KD diets.
• Performed survival analysis, histological examination, proteomic analysis, and serum cytokine profiling.

Main Results:

• KD significantly reduced survival (26 days) vs. standard diet (87 days).
• HFD also reduced survival (35 days) vs. standard diet.
• KD and HFD induced aggressive PDAC with fibrosis and altered signaling pathways (PI3K-Akt-mTOR, EGFR).

Conclusions:

• Dietary lipid enrichment before oncogenic Kras activation accelerates early pancreatic neoplasia.
• KD and HFD promote a pro-tumorigenic microenvironment.
• Caution is advised regarding KD use in individuals at high risk for pancreatic cancer.