The effects of dihimo-γ-linolenic acid (DGLA) in mouse macrophages and a zebrafish model of gut inflammation

Dihomo-γ-linolenic acid (DGLA) is an omega-6 LC-PUFA known for its anti-inflammatory, immuno-modulatory, and anti-proliferative properties. Using RAW 264.7 macrophages, we found that DGLA induced the elevated production of the anti-inflammatory prostaglandin E1, and decreased production of nitric oxide upon challenge with LPS. This effect was associated with decreasing expression of nitric oxide synthase and arginase genes, suggesting an effect on the L-arginine-nitric oxide system. We are using a zebrafish model of Inflammatory Bowel Disease (chemically induced colitis) to assess the effects of interventions with DGLA-enriched diets on anti- and pro-inflammatory gene expression in the gut, as well as histopathological changes in the gut mucosa. Biomass of a unique DGLA-producing microalga was used as a dietary supplement along with commercial DGLA. Fish were fed with the experimental diets for four weeks. Gut inflammation was induced by intubation with 120 µM TNBS; gut samples were collected before and 24-h post-induction for analyses of gene expression and histological analysis. The results showed a differential transcriptional response in the different treatment groups for genes involved in the function of the mucosal barrier, including antioxidant, COX and inflammatory genes. For example, diets enriched with DGLA in different forms increased the expression of hepcidin, an antimicrobial peptide. The high inclusion level (15%) of nutrient-replete microalga showed an outstanding effect, increasing the transcript levels of lysozyme, IL8, COX1, TNF, and iL1b after feeding. A quantitative histomorphometry of key gut features before and after TNBS treatment is underway to correlate gene expression with alterations in gut morphology.