Prevention of damage to the cholinergic pathway in bone marrow cells after short-term exposure to high fat diet: the effect of supplementation with omega-3 fatty acid (EPA and DHA)

Abstract

Inflammatory signals from the periphery are transmitted to the central nervous system through the afferent arm of the vagus nerve and culminate in an anti-inflammatory response through the efferent arm of the vagus nerve. This mechanism is known as cholinergic anti-inflammatory reflex and promotes the release of acetylcholine by the terminal nerve that activates nicotinic cholinergic receptors (±7nAChR) in target cells.Activation of these receptors reduces the production of proinflammatory cytokines in different cell types. The pharmacological activation of the receptor leads to a reduction in inflammation and an increase in survival in a mouse model of sepsis. Data from our group show that animals that consumed a short-term high fat diet present impairment of the cholinergic anti-inflammatory response with reduction of ±7nAChR receptor expression in bone marrow cells. This alteration of ±7nAChR receptor expression in monocytes seems to favor its polarization to macrophages with inflammatory profile (M1 macrophages type). In other inflammatory models investigated, such as exposure to lipopolysaccharide (LPS) or palmitate, the reduction of ±7nAChR expression is evident, suggesting that the reduction in receptor amount has some relation to the activation of inflammatory pathways. Omega3 polyunsaturated fatty acids have an important anti-inflammatory role trough the interaction with GPR-120 type receptors located in the membrane of macrophages, for example. Thus, we hypothesized that É3 supplementation can prevent the damage caused by the consumption of high fat diet and favor the polarization of the monocytes to the M2 anti-inflammatory profile. To test this hypothesis Swiss male mice will previously be supplemented with w3 fatty acid for 17 days and consumed diet rich in saturated fats from the 15th to the 17th day. After the sacrifice and isolation of bone marrow cells, the number of cells obtained, ±7nAChR expression, the proinflammatory cytokines TNF-±, IL1-² and IL-6 and chemokines CXCL2, CX3CL1, CCL2 as the phosphorylation of the protein STAT3 signaling will be evaluated. Expression analyzes will be performed by real-time PCR, Western Blotting and ELISA. To evaluate the improvement in the inflammatory response, a survival test will be performed in mouse after induction of sepsis through the puncture and cecum ligation (CLP) surgery.