Dietary n-3 polyunsaturated fatty acids (PUFA) decrease obesity-associated Th17 cell-mediated inflammation during...

Area of Science:

• Immunology
• Nutrition Science
• Gastroenterology

Background:

• Obesity-associated inflammation exacerbates colitis severity.
• T helper 17 (Th17) cells play a significant role in obesity-driven inflammation and colitis.
• Targeting inflammatory pathways is crucial for managing concurrent obesity and colitis.

Purpose of the Study:

• To investigate the effects of n-3 polyunsaturated fatty acids (PUFAs) on immune cell subsets and inflammatory gene expression in a mouse model of concurrent obesity and colitis.
• To determine if n-3 PUFA supplementation can ameliorate the disease phenotype in obese mice with colitis.

Main Methods:

• Mice were fed a high-fat (HF) diet or an isocaloric HF diet supplemented with fish oil (HF-FO) for 12 weeks to induce obesity.
• Colitis was induced using trinitrobenzene sulfonic acid (TNBS) enema.
• Immune cell subsets, inflammatory biomarkers, and gene expression were analyzed in visceral adipose tissue, colon, and spleen.

Main Results:

• The HF-FO diet improved the obese phenotype by reducing serum leptin and resistin, and decreasing inflammatory cytokine mRNA expression and M1 macrophage content in adipose tissue.
• HF-FO diet significantly reduced colitis severity and suppressed colonic mRNA expression of Th17 cell-related factors (RORγτ, IL-6, IL-17A, IL-17F, IL-21, IL-23, IFNγ).
• n-3 PUFA supplementation decreased the percentage of splenic Th17 and Th1 cells and suppressed Th17 cell differentiation in vitro.

Conclusions:

• n-3 PUFAs effectively suppress Th1/Th17 cells and inflammatory macrophage subsets in obese mice with colitis.
• Dietary fish oil reconfigures inflammatory gene expression profiles across multiple tissues, mitigating disease severity.
• n-3 PUFA supplementation represents a promising therapeutic approach for managing inflammation in obesity and colitis.