Fatty acid synthase inhibitor C75 ameliorates experimental colitis

Area of Science:

• Biochemistry
• Immunology
• Gastroenterology

Background:

• Abnormal lipid metabolism, particularly fatty acid synthase (FASN) overexpression, is linked to inflammatory bowel disease (IBD) development.
• C75 is a synthetic compound that inhibits FASN activity.

Purpose of the Study:

• To investigate the therapeutic potential of C75 in reducing the severity of experimental colitis.
• To evaluate the effects of C75 on clinical parameters, colon damage, apoptosis, and inflammatory pathways in a dextran sodium sulfate (DSS)-induced colitis model.

Main Methods:

• Male C57BL/6 mice were induced with colitis using 4% DSS for 7 days.
• C75 (5 mg/kg) or vehicle (DMSO) was administered intraperitoneally from day 2 to 6.
• Clinical and histological parameters, colon length, apoptosis, and inflammatory mediators were assessed on day 8.

Main Results:

• C75 treatment significantly reduced body weight loss, fecal bleeding, diarrhea, and colon histological damage compared to vehicle.
• C75 administration improved colon shortening and protected against DSS-induced apoptosis by inhibiting caspase-3 activity.
• C75 downregulated key inflammatory mediators, including chemokines, cytokines (TNF-α, IL-1β, IL-6), and enzymes like COX-2 and iNOS, while inhibiting IκB degradation.

Conclusions:

• C75 effectively alleviates colon damage and suppresses inflammatory pathway activation in DSS-induced colitis.
• Inhibition of fatty acid synthase (FASN) by C75 demonstrates potential as a therapeutic strategy for inflammatory bowel disease (IBD).