Additionally to anti-inflammatory effects, correlated with down-regulation of IL-6 and TNF-α expression in liver, n-3 PUFAs also exhibited triglyceridemia lowering effects in diabetic rats via modulation of PPAR-α (Devarshi et al., 2013; Ghadge et al., 2016). Additionally, Lee et al. demonstrated that a diet with a high n-6/n-3 PUFAs ratio (~9) induced dysbacteriosis of the gut microbiota in obesity-induced T2DM or high-fat-diet treated rats, while a low ratio (~3) enhanced blood glucose homeostasis (Lee et al., 2019). The outcomes of the most recent animal studies are summarized in Table 5 .
Table 5 Mittigating inflammation in animal model studies – effects of PUFAs.
Tested compound(s) Animal model Main anti-inflammatory findings References
n-3 PUFA (fish oil or mix fish and olive oil or flaxseed oil) TNBS colitis ↓IL-1β; IL-12p70; ↓IL-6; ↓TNFα; ↑PGE3,↑ TXB3; ↑ LTB5 Bosco et al. (2013)
TNBS colitis ↓colon iNOS, ↓COX-2 expression, ↓IL-6, ↓LTB4, ↓TNFα production Charpentier et al. (2018)
DSS colitis ↓TNF-α; ↓ COX-2; ↑anti-inflammatory PG; Sharma et al. (2019)
Carrageenan induced inflammation ↓TNF-α; ↓ IL-6 Zadeh-Ardabili and Rad (2019)
STZ- diabetic rats ↑ gene expression PPRγ; ↓ NF-κB activity Ghadge et al. (2016)
STZ- diabetic rats ↓TNF-α; ↓ IL-6 Lee et al. (2019)
STZ-NIC diabetic rats ↑ PPAR-α only by flaxseed oil; both (flaxseed oil and fish oil):↑ D5 and D6 desaturases; ↓TNF-α; ↓ IL-6; Devarshi et al. (2013)
STZ-NIC diabetic rats ↑ renal SOD-1; ↑ GPx-1 expression; ↑ CAT; ↓ renal AGEs formation ↓AGE protein expression; ↓ IL-6; ↓ NF-κB expression Jangale et al. (2016)
STZ-NIC diabetic rats ↓ IL-1β; ↓TNFα; ↓IL-6; ↓IL-17 A; ↓MDA Zhu et al. (2020)
Wistar rats ↓ IL-6; ↓ TNF-α; ↓IL- 10 receptor Pimentel et al. (2013)
C57BL/6 mice ↓ NF-κB expression; ↓ IL-6; ↓ TNF-α Bargut et al. (2015)
EPA monogliceride DSS colitis ↓PMN infiltration; ↓ NF-κB activity; ↓IL-1β; ↓TNF-α; ↓ IL-6; ↓expression of COX2 in colon Morin et al. (2016)
ALA TNBS colitis ↓ IP-8, ↓ LTB4, ↓ colon NF-κB DNA binding activity Hassan et al. (2010)
EPA vs. DHA high-fructose fed C57BL/6J mice ↓ TNF-alpha and IL-6 gene expressions; ↓MCP-1 pERK and NFkB protein expressions Bargut et al. (2017)
EPA free fatty acid APCMin/+ FAP model ↓ COX-2 expression; ↑ EPA tissue uptake; ↓ lipid peroxidation Fini et al. (2010)
CAC model C57BL/6J mouse ↓PGE2; ↑ EPA tissue uptake Piazzi et al. (2014)
Endogenous conversion n-6 into n-3 PUFA CAC modelFat-1 mouse ↓ COX-2 expression; ↓ NF-κB activity; ↓PGE2 Han et al. (2016)
Chronic arthritisFat-1 mouse vs WT mouse ↓ IL-17; ↑mRNA expression of Foxp3 (in Fat-1 mouse) Kim et al. (2018)
AT-RvD1 DSS colitis/TNBS colitis ↓PMN infiltration; ↓ NF-κB activity and mRNA expression; ↓IL-1β; ↓MIP-2; ↓mRNA expression of VCAM-1, ICAM-1 Bento et al. (2011)
Adjuvant-induced arthritis ↓TNF-α; IL-1β Lima-Garcia et al. (2011)
RvD2 DSS colitis ↓IL-1β; ↓ murine KC (IL-8 human homolog) Campbell et al. (2010)
TNBS colitis ↓PMN infiltration; ↓ NF-κB activity and mRNA expression; ↓IL-1β; ↓MIP-2; ↓mRNA expression of VCAM-1, ICAM-1 Bento et al. (2011)
RvE1 DSS colitis ↓PMN infiltration; ↓TNF-α; ↓mRNA expression of IL-6, TNFα, IL-1β Ishida et al. (2010)
Collagen-induced arthritis No statistical significant effect on TNF-α de Molon et al. (2019)
RvD5 DSS colitis ↓PMN infiltration; ↓TNF-α; ↓ IL-6; ↓IL-1β; Gobbetti et al. (2017)
MaR1 DSS colitis/TNBS colitis ↓PMN infiltration; ↓ NF-κB activity; ↓IL-1β; ↓TNF-α; ↓ IL-6; ↓mRNA expression of ICAM-1 Marcon et al. (2013)
PD1 DSS colitis ↓PMN infiltration; ↓IL-1β only partially Gobbetti et al. (2017)
CAC – colitis associated cancer; CAT – catalase DSS – dextran sulfate sodium; GPx – glutathione peroxidase NIC – Nicotinamide; PD – protectin; SOD – superoxide dismutase; STZ – Streptozotocin; TNBS – trinitrobenzene sulphonic acid; EPA – Eicosapentaenoic Acid; DHA – Docosahexaenoic Acid; TNF – α-Tumour Necrosis Factor alpha; LTB – Leukotriene, PPAR – peroxisome proliferator-activated receptor; COX – cyclooxygenase; AGE – advanced glycation end products; TXB – Thromboxane; PG – prostaglandins; ICAM – Intercellular Adhesion Molecule; VCAM – Vascular Cell Adhesion molecule; IL – Interleukin; NF-κB, nuclear factor kappa B; PMN – polymorphonuclear leukocyte; MIP-2 –macrophage inflammatory protein 2; IP-8 – Isoprostane-8; Foxp3 – Forkhead box P3; pERK – protein kinase RNA-like endoplasmic reticulum kinase; MCP-1 – Monocyte chemoattractant protein-1; murine KC – murine chemokine.