Fish oil and flax seed oil supplemented diets increase FFAR4 expression in the rat colon

Abstract

Background and objective Omega-3 fatty acids, such as α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are polyunsaturated fatty acids (PUFA) that have long been associated with anti-inflammatory activity and general benefit toward human health. Over the last decade, the identification of a family of cell-surface G protein-coupled receptors that bind and are activated by free-fatty acids, including omega-3 fatty acids, suggests that many effects of PUFA are receptor-mediated. One such receptor, free-fatty acid receptor-4 (FFAR4), previously described as GPR120, has been shown to modulate anti-inflammatory and insulin-sensitizing effects in response to PUFA such as ALA and DHA. Additionally, FFAR4 stimulates secretion of the insulin secretagogue glucagon like peptide-1 (GLP-1) from the GI tract and acts as a dietary sensor to regulate energy availability. The aim of the current study was to assess the effects of dietary omega-3 fatty acid supplementation on FFAR4 expression in the rat colon. Methods Sprague-Dawley rats were fed control soybean oil diets or alternatively, diets supplemented with either fish oil, which is enriched in DHA and EPA, or flaxseed oil, which is enriched in ALA, for seven weeks. GLP-1 and blood glucose levels were monitored weekly and at the end of the study period, expression of FFAR4 and the inflammatory marker TNF–α was assessed. Results Our findings indicate that GLP-1 and blood glucose levels were unaffected by omega-3 supplementation, however, animals that were fed fish or flaxseed oil-supplemented diets had significantly heightened colonic FFAR4 and actin expression, and reduced expression of the pro-inflammatory cytokine TNF-α compared to animals fed control diets. Conclusions These results suggest that similar to ingestion of other fats, dietary intake of omega-3 fatty acids can alter FFAR4 expression within the colon.

Effect of different levels of feed restriction and fish oil fatty acid supplementation on fat deposition by using different techniques, plasma levels and mRNA expression of several adipokines in broiler breeder hens

“…We found a decreasing effect of fish oil supplementation onthe mRNA expression of FFAR4 in liver, as well as an increase of lipogenesis ( FASN ) and glucose transporter ( GLUT8 ) associated with an increase of ADIPOQ expression. This inhibitory effect of fish oil supplementation on FFAR4 expression in liver is in contrast to data previously reported for the rat colon in response to chronic supplementation of diets with 10% fish oil for a period of seven weeks [ 48 ]. However, Cornall and colleagues reported a tissue-specific upregulation of FFAR4 expression in rats, such that high-fat diets increased FFAR4 expression in cardiac muscle and EDL skeletal muscle, but not in liver or soleus skeletal muscle [ 49 ].…”

α-Linolenic acid increases the G0/G1 switch gene 2 mRNA expression in peripheral blood mononuclear cells from obese patients: a pilot study

“…In this study, we found that 12-week treatment with ALA significantly increased GPR120 gene expression of PBMC and decreased plasma IL-6 and TNF-α levels in obese patients. Our results are compatible with a recent report [ 32 ], showing that flaxseed oil enriched in ALA significantly increased colonic FFAR4 expression and reduced expression of the pro-inflammatory cytokine TNF-α. In cultured mouse adipocytes, EPA upregulated vascular endothelial growth factor-A (VEGF-A), a known PPAR-γ target gene, mRNA expression by inducing PPAR-γ binding to PPRE in VEGF-A promoter region [ 33 ].…”

Free-fatty acid receptor-4 (GPR120): Cellular and molecular function and its role in metabolic disorders

“…Given the dense expression of FFA4 in the GI tract, it is of interest that studies in animals fed high fat diets reveal upregulation of FFA4 expression in variety of tissues, including within the GI tract. FFA4 transcript and protein expression in the intestines were increased in diet-induced obese rats compared to the diet-resistant genotype [37], while results from Cheshmehkani and colleagues confirm that FFA4 expression in the colon is also upregulated in diets supplemented with n-3 fatty acids [38]. Still, others have shown that FFA4 transcript and the number of FFA4-positive enteroendocrine cells in the mouse gastric corpus increased in as little as three weeks in animals fed a high fat diet, while the FFA4-positive cells in the gastric antrum was reduced, suggesting that dietary fat regulation of FFA4 expression is cell-type specific [39].…”