Dietary Stearic Acid Accelerates Intestinal Tumorigenesis via Fatty Acid-binding Protein 5 Without Promoting Obesity.

Area of Science:

• Gastroenterology and Hepatology
• Oncology
• Molecular Biology

Background:

• Dietary fat intake is a known risk factor for intestinal cancer.
• The specific impact of different fatty acid compositions on intestinal tumorigenesis remains unclear.

Purpose of the Study:

• To investigate the differential effects of linoleic acid (LA)-rich and stearic acid (SA)-rich high-fat diets (HFDs) on intestinal carcinogenesis.
• To elucidate the role of fatty acid-binding protein 5 (FABP5) in dietary fatty acid-mediated colorectal cancer (CRC) development.

Main Methods:

• Utilized Apc^Min/+ mice and azoxymethane/dextran sulfate sodium-induced CRC mouse models fed LA-rich or SA-rich HFDs.
• Employed fatty acid-binding protein 5 (FABP5) knockout mice and a FABP5 inhibitor (SBFI-26) to assess FABP5's contribution.
• Examined effects on epithelial cell proliferation, Paneth cell differentiation, and intestinal stem cell populations in murine and human organoids.

Main Results:

• SA-rich HFD accelerated CRC development more than LA-rich HFD, with less pronounced obesity.
• SA significantly increased epithelial cell proliferation and Paneth cell differentiation compared to LA.
• SA promoted crypt formation in organoids, and this effect, along with tumorigenesis, was suppressed by FABP5 inhibition.

Conclusions:

• Dietary stearic acid promotes colorectal cancer development through fatty acid-binding protein 5.
• This promotion of intestinal tumorigenesis by SA occurs independently of significant obesity induction.